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Cochrane Database of Systematic Reviews Review - Intervention

Different classes of antibiotics given to women routinely for preventing infection at caesarean section

Authors' declarations of interest

Version published: 04 March 2021 Version history

https://doi.org/10.1002/14651858.CD008726.pub3
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Background

Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects. 

Objectives

To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant.

Search methods

For this 2020 update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies.

Selection criteria

We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section.  RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi‐RCTs and cross‐over trials. Cluster‐RCTs were eligible for inclusion but none were identified.

Data collection and analysis

Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach.

Main results

We included 39 studies, with 33 providing data (8073 women). Thirty‐two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately.

We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'.   We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides plus aminoglycosides'.

Twenty‐seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub‐classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section.

Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1st and 2nd generation) versus non‐antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3rd generation) versus non‐antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled.

For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported.

Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events.

In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low‐certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low‐certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low‐certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies.

For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer‐term maternal outcomes, or on any infant outcomes.

Authors' conclusions

Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post‐operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Comparing different types of antibiotics given routinely to women at caesarean section to reduce infections

What is the issue?

We wanted to find out if giving specific types of antibiotics routinely at caesarean sections reduced the number of women and babies with infections, when compared with other types of antibiotics. We also looked to see if there were differences in adverse effects. The main types of antibiotics we considered were ones which target infections most commonly seen after giving birth, so we looked mainly at cephalosporins versus penicillins. We collected and analysed all relevant studies (randomised controlled trials) to answer this question (date of latest search 2 December 2019).

Why is this important?

Women undergoing caesarean section have an increased likelihood of infection compared with women giving birth vaginally. These infections can come from the urine, the surgical incision, or occur in the lining of the womb (endometritis). Infections can be serious, causing, for example, an abscess in the pelvis or infection in the blood. Very occasionally they can lead to a mother's death, particularly in low‐resource settings. Good surgical techniques are important to reduce infection, along with the use of skin antiseptics and giving antibiotics before the initiation of the caesarean section. Antibiotics can, however, cause adverse effects in the mother, such as nausea, vomiting, skin rash and in some rare cases allergic reactions. The mother and the baby can develop thrush (candida). Antibiotics given to women around the time of giving birth can also change the baby's gut flora and may interfere with the baby's developing immune system.

What evidence did we find?

We included 39 studies, of which 33 studies involving 8073 women and their babies provided data. The quality of the individual studies was generally unclear, which led to overall low or very low certainty of the evidence. Three of the 33 studies were undertaken with drug company funding. Most of the studies administered antibiotics at or after cord clamping, although practice now often gives antibiotics before skin incision.

Eight studies with data on 1540 women reported on antistaphylococcal cephalosporins (first and second generation) versus broad spectrum penicillins plus betalactamase inhibitors. We found that these antibiotics may be as effective as each other in reducing endometritis and maternal fever. We were uncertain which antibiotic performed better for wound infection, urinary tract infection, and maternal adverse effects such as nausea, vomiting, diarrhoea and skin rash. We did not find any evidence on longer‐term outcomes for mothers once they left hospital, or on any outcomes for babies. Only one small study (75 women) reported on blood infection (sepsis) in mothers, with too few events to identify any clear differences between the antibiotics.

We identified no studies with evidence on antistaphylococcal cephalosporins versus lincosamides, nor antistaphylococcal cephalosporins versus lincosamides plus aminoglycosides. The other studies looked at a very large number of different comparisons with insufficient data to come to any firm conclusions about specific comparisons.

What does this mean?

At caesarean sections, antistaphylococcal cephalosporins and penicillins plus betalactamase inhibitors may be similarly effective at preventing infections for the mother, although we did not find clear evidence for many important outcomes. In particular, we found no evidence describing the effects of these antibiotics on babies, nor any longer‐term effects on women and children. This is particularly concerning for the studies giving the antibiotics prior to the surgical incision, as these antibiotics may reach the baby. For the other comparisons included in this review, data were sparse. Many studies were old and lacked information on study design and important outcomes, often including small numbers of women and few events. Research on drug‐resistant antibiotics needs to be considered as well.

Authors' conclusions

Implications for practice

Best current evidence suggests that there may be little or no difference in short‐term outcomes between antistaphylococcal cephalosporins (1st and 2nd generation) and 'broad spectrum penicillins plus betalactamase inhibitors' as prophylaxis for women undergoing caesarean section, although the impact on post‐discharge infections and outcomes for the infant are unknown, as is the impact on bacterial resistance. All are critical to decision‐making. The use of any antibiotic needs to be made on an individual basis, taking into account other medication the mother may be on, comorbidities and history of allergic reactions. The impact on the baby, for which there is no formal evidence, also needs to be considered, as does bacterial resistance. More costly extended‐spectrum penicillins, second or third‐generation cephalosporins, and combination regimens have not been demonstrated to be more effective, but there are few data upon which to make a clear judgement.

Considering that we did not identify differences between antibiotic regimens in terms of the measured outcomes indicative of effectiveness and safety, the decision of what antibiotic to use will depend on the woman's sensitivity to specific antibiotics, the physician's experience, the adverse events, the prevalence of pathogenic organisms according to previous epidemiological studies (if available), the availability and the costs in the different scenarios.

Implications for research

There is a need for good‐quality trials to assess the most effective antibiotic to use at caesarean section and it is critical that short and long term outcomes for the baby, and post‐discharge outcomes for the mother, are more comprehensively assessed. In particular, trials need to do a better job of investigating possible harms; for instance relating to long‐term adverse effects of antibiotic exposure on the newborn's developing immune system and microbiome, especially in light of increasing rates of caesarean section and increasingly routine use of antibiotics pre‐incision. Trials could include the outcomes identified for this review, in particular outcomes on the baby and post‐discharge infections for the mother.

There is also a need for trials to differentiate between investigation of the most effective and safe of antibiotics at the most urgent caesarean deliveries (where infection control measures are likely to be compromised), and their use as part of the infection prevention package in surgeries that are scheduled. It would be helpful if triallists could employ a distinction between these different situations that is more precise than 'elective versus non‐elective', for instance employing the RCOG four‐fold definition of caesarean emergency, and clearly separating category 1 (the most urgent) surgeries from other scenarios (RCOG 2011).

The impact of routine antibiotics at caesarean section on antibiotic resistance needs to be investigated with some urgency, but can probably not be undertaken within a Cochrane Review due to the need for alternative methodology.

The absence of evidence for two of our main comparisons indicates that there is also a gap in knowledge regarding the comparability of 1st generation cephalosporins to clindamycin or clindamycin plus aminoglycoside, despite the fact that these are the recommended alternative regimens in several major guidelines (e.g. ACOG 2018; IDSA 2013; SOGC 2017).

Several studies (both complete and ongoing) identified by our 2019 search compared a combination of a 1st or 2nd generation cephalosporin plus azithromycin versus the same cephalosporin, with study authors citing an interest in investigating adjunctive azithromycin because it targets ureaplasma. These studies would at present fall within the scope of a different Cochrane Review (Different regimens of cephalosporin antibiotic given to women routinely for preventing infection after caesarean section) and were therefore excluded from our review, however that title remains vacant. For future updates of the present review, it may be important to revisit the scope to reflect shifts in research and clinical practice globally (e.g. to consider to including these studies).

Summary of findings

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Summary of findings 1. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section

Patient or population: all women undergoing caesarean section
Setting: Hospital (Greece, India, Thailand, USA)
Intervention: antistaphylococcal cephalosporins 1st and 2nd generation (C1 and C2)
Comparison: broad spectrum penicillins plus betalactamase inhibitors (P2+)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with broad spectrum penicillins plus betalactamase inhibitors (P2+)

Risk with Antistaphylococcal cephalosporins (1st and 2nd generation (C1 and C2)

Maternal sepsis

Study population

RR 2.37
(0.10 to 56.41)

75
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

0 per 1000

0 per 1000
(0 to 0)

Maternal endometritis

Study population

RR 1.10
(0.76 to 1.60)

1161
(7 RCTs)

⊕⊕⊝⊝
LOW 1 3

78 per 1000

86 per 1000
(60 to 125)

Infant sepsis

Study population

‐

(0 studies)

‐

No included studies reported on this outcome

see comment

see comment

Infant oral thrush

Study population

‐

(0 studies)

‐

No included studies reported on this outcome

see comment

see comment

Maternal wound infection

Study population

RR 0.78
(0.32 to 1.90)

543
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 4 5

38 per 1000

29 per 1000
(12 to 71)

Maternal urinary tract infection

Study population

RR 0.64
(0.11 to 3.73)

496
(4 RCTs)

⊕⊝⊝⊝
VERY LOW
6 7 8

51 per 1000

33 per 1000
(6 to 190)

Maternal composite adverse effects

Study population

RR 0.96
(0.09 to 10.50)

468
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 4 5

5 per 1000

5 per 1000
(0 to 56)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

1 All of pooled effect provided by study or studies at moderate risk of selection bias. Downgrade ‐1.

2 Single study with small sample size and few events. Wide confidence interval including both appreciable reduction and appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins. The reported data are for bacteriaemia, not sepsis. Although bacteriaemia is usually accompanied by sepsis, there is the possibility of indirectness for this outcome. Downgrade ‐2.

3 Wide confidence interval including appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins, whilst also including no difference in effect. Downgrade ‐1.

4 Majority of pooled effect provided by studies at moderate risk of selection bias or detection bias. Downgrade ‐1.

5 Few events. Wide confidence interval including both appreciable reduction and appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins. Downgrade ‐2.

6 Majority of pooled effect provided by studies at moderate risk of bias due to lack of information about random sequence generation and concealment of allocation. Downgrade ‐1.

7 Severe unexplained statistical heterogeneity (I2 = 66%, P value for Chi2 test = 0.05). Downgrade ‐1.

8 Few events. Downgrade ‐1.

Background

The incidence of caesarean sections is increasing annually, with a global estimate of 29.7 million births by caesarean section (20.1% of live births) in 2015, up from 12% in 2000 (Boerma 2018). Rates of caesarean section differ widely by region, from 4.1% in parts of Africa to 44.3% in some areas of Latin America (Boerma 2018). Women undergoing caesarean section have an increased risk of postoperative infection and infectious morbidity compared with women giving birth vaginally (Declercq 2007), therefore the large and potentially increasing number of infections worldwide is a major concern.

Description of the condition

Caesarean sections have been shown to have nearly five times the risk of postpartum infection as vaginal births (and this is with a policy of antibiotic prophylaxis at caesarean section), and just over 75% occur after hospital discharge (Leth 2009). The infectious complications that can occur after caesarean birth include infections of the wound/incision, endometritis (infection of the lining of the uterus) and urinary tract infection (UTI), although fever can occur after any operation and is not necessarily an indicator of infection (Mascarello 2017; van Dillen 2010). However, there can occasionally be more serious infectious complications such as pelvic abscess (collection of pus in the pelvis), bacteraemia (bacterial infection in the blood), sepsis (organ dysfunction resulting from infection), and its most severe form septic shock, necrotising fasciitis (tissue destruction in the abdominal wall), and septic pelvic vein thrombophlebitis (inflammation and infection of the veins in the pelvis). These more serious infectious complications can lead to maternal mortality.

Description of the intervention

The potential for prophylactic antibiotics to reduce the incidence of maternal infectious morbidity following caesarean section has now been systematically investigated (Hofmeyr 2010; Smaill 2014). Although evidence has existed for some time to support this practice (Smaill 2014; Wilson 2018), it is not clear whether any one particular agent, dose or route of administration is superior. Many different drug regimens have been reported to be effective in decreasing immediate postoperative infectious morbidity. To date, various penicillins (ampicillin, ticarcillin, mezlocillin, piperacillin), cephalosporins (cefazolin, cephalothin, ceforanide, cefonicid, cefuroxime, ceftazidime, cefoxitin, cefamandole, cephradine, cefotetan, cefotaxime), fluoroquinolones, etc. have been used for caesarean section prophylaxis and overall they have demonstrated some efficacy either alone or in combination with another drug (Smaill 2008). Some of these drugs have activity against a narrow range of potential pathogens (e.g. metronidazole, gentamicin), others have additional specific anaerobic activity (e.g. cefoxitin and cefotetan), and yet others have very broad‐spectrum coverage (imipenem). Their pharmacokinetic properties (e.g. serum half‐life) also differ. Some drugs used in the past are now associated with bacterial resistance (Martinez de Tejada 2014). Despite variability in local policies, the American College of Obstetricians and Gynecologists (ACOG 2018), Infectious Diseases Society of America (IDSA 2013), and the Canadian Society of Obstetrics and Gynaecology (SOGC 2017) have recommended the use of cefazolin or other first‐generation cephalosporins as first choice for prophylaxis at caesarean section. In the UK, the Royal College of Obstetricians and Gynaecologists recommend prophylactic antibiotics before skin incision that are effective against endometritis, UTI and wound infections, however they advise against co‐amoxyclav (amoxicillin plus clavulanic acid) due to an increase in risk of necrotising enterocolitis for babies exposed to this antibiotic (RCOG 2011).

In addition to the choice of drug, there are differences in the route and the timing of administration of prophylactic antibiotics. As well as systemic administration (intravenous, intramuscular or oral), use of intra‐operative irrigation of the uterus and peritoneal cavity with an antibiotic solution has been reported. While some guidelines recommend multiple doses of antibiotics, a single dose at the time of the procedure may be adequate. These considerations will be covered in other Cochrane Reviews ‐ see Differences between protocol and review for details.

How the intervention might work

Since penicillin was introduced during the 1940s, scientists have developed numerous other antibiotics. Today, over 100 different antibiotics are available. For the prevention of surgical infections, it is generally considered that sound surgical technique is important along with skin antiseptics and the use of antibiotics (Martin 2018; Walsh 2010). Antibiotics act by either killing bacteria (bactericidal) or inhibiting bacterial replication (bacteriostatic), but the large variety of different types of bacteria mean a large variety of possible antibiotics may be used (Kapoor 2017).

Classification of antibiotics

Antibiotics can be classified in a number of ways, but classifying by chemical structure is useful because antibiotics within a structural class will generally have similar patterns of effectiveness, toxicity and allergic potential (Bayarski 2006; eMedExpert 2009; Goodman 2008). The most commonly used types of antibiotics for surgical prophylaxis are penicillins with or without betalactamase inhibitors, cephalosporins, aminoglycosides, lincosamide, fluoroquinolones, carbapenems, and macrolides. Each class includes many drugs (Table 1). Penicillins have a common structure which they share with cephalosporins and carbapenems, the betalactam ring. Both penicillins and cephalosporins are bactericidal, acting through inhibiting cell wall synthesis (Letourneau 2020a). Penicillins are grouped into three types and cephalosporins are grouped into five generations with each newer generation having a broader spectrum of activity (Letourneau 2020b; Letourneau 2020d). Fluoroquinolones are synthetic rather than derived from bacteria, and interfere with the ability of bacteria to make DNA. These newer fluoroquinolones are broad‐spectrum bacteriocidal drugs chemically unrelated to penicillins or cephalosporins. Macrolides are derived from streptomyces bacteria and are also bacteriostatic in action, binding to bacterial ribosomes. Aminoglycosides are relatively broad spectrum antibiotics usually used in combination with other antibiotics such as beta‐lactams (Drew 2020).

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Table 1. Classification of antibiotics

Penicillins (P)

Penicillins consist of a thiazolidine ring connected to a B‐lactam ring to which is attached to a side chain. The penicillin nucleus itself is the chief structural requirement for biological activity. Penicillins are the oldest class of antibiotics and function by inhibiting cell wall synthesis (bactericidal).

Class or sub‐class name and detail

Examples

Spectrum

Natural penicillins (P1) are based on the original penicillin‐G structure (also known as first‐generation penicillins)

Penicillin G (benzyl penicillin, crystalline penicillin); Procaine; Penicillin V; Benzathine.

Gram‐positive: non‐betalactamase producing gram‐positive cocci (including viridans streptococci, group A streptococci, Streptococcus pneumoniae, anaerobic Streptococcus), Enterococcus spp., non‐penicillinase producing strains of Staphylococcus aureus, coagulase negative Staphylococcus aureus, Clostridium spp. (excluding C. difficile), Actinomyces spp

Gram‐negative:Neisseria meningitides, non‐penicillinase producing Neisseria gonorrhoea, Pasteurella multocida

Broad spectrum penicillins(P2) which are effective against a wider range of bacteria

Second‐generation penicillins:

Aminopenicillins; Ampicillin; Amoxicillin.

Gram‐positive:Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes.

Gram negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae Anaerobes: Clostridium spp

Third‐generation penicillins:
Carbenicillin; Ticarcillin.

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes.

Gram‐negative: Escherichia coli, Proteus mirabilis, Salmonella, Shigella, Haemophilus influenzae, Pseudomonas aeruginosa, Acinetobacter spp

Anaerobes: Clostridium spp

Fourth‐generation penicillins:
Piperacillin; Mezlocillin.

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus.

Gram‐negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae

Anaerobes: Clostridium spp, Bacteroides fragilis

Penicillins plus betalactamase inhibitors (P2+) are active against gram‐positive, gram‐negative and anaerobic bacteria, including S.aureus, Enterococci, Streptococci, many Enterobacterales and Bacteroides spp

Co‐amoxyclav = amoxicillin + clavulanic acid (Trade names include: Augmentin; Clavamox; Tyclav)
Ampicillin + sulbactam (Trade names include: Ampictam; Unasyn)
Timentin = ticarcillin + clavulanate

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus.

Gram‐negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae

Anaerobes: Clostridium spp, Bacteroides fragilis

Antistaphylococcal penicillins(P3) are active even in the presence of the bacterial enzyme that inactivates most natural penicillins (also known as penicillinase‐resistant penicillins)

Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin.

Staphylococcus aureus

Cephalosporins (C)

Cephalosporins have a similar basic structure to penicillins but with different side chains. They function by inhibiting cell wall synthesis.

First‐generation cephalosporins (C1)

Cephalothin; cefazolin; cephapirin; cephradine; cephalexin; cefadroxil.

Gram‐positive: (Streptococcus spp, Staphylococcus aureus) Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae

Anaerobes: except Bacteroides

Second‐generation cephalosporins (C2)

Cefoxitin; cefaclor; cefuroxime; cefotetan; cefprozil; cefamandole, cefonicid; ceforanide, cefotiam.

Gram‐positive: (Streptococcus spp, Staphylococcus aureus) Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae.

Anaerobes: including Bacteroides (Cephamycins)

Third‐generation cephalosporins (C3)

Cefotaxime; ceftizoxime; ceftriaxone; cefpodoxime; cefditoren; ceftibuten; ceftazidime; cefcapene; cefdaloxime; cefetamet; cefixime; cefmenoxime; cefodizime; cefoperazone; cefpimizole.

Gram‐negative: Enterobacterales, Neisseria spp, Haemophilus spp

Gram‐positive: Streptococcus spp

Anaerobes:Bacteroides fragilis, Clostridium spp, Peptostreptococcus spp, Prevotella sp

Fourth‐generation cephalosporins (C4)

Cefepime; cefpirome; cefclidine; cefluprenam; cefozopran; cefquinome.

Gram‐negatives: Enterobacterales, Neisseria spp, Haemophilus spp, Acinetobacter spp, Pseudomonas aeruginosa
Gram‐positive:Staphylococcus aureus, Streptococcus spp

Cephalosporin plus betalactamase inhibitors (C+)

Ceftolozane‐tazobactam; ceftazidime‐avibactam.

Ceftolozane‐tazobactam

Gram‐negative:Enterobacterales, P aeruginosa, Gram‐positive: limited activity against streptococci, general low activity against staphilococcal and enterococcal species.

Ceftzidime‐avibactam extends the spectrum of ceftazidime against AmpC beta‐lactamase, ESBL and some specific carbapenemases

Other classes of antibiotics

Aminoglycosides (A) are first‐line therapy for a limited number of very specific, often historically prominent infections, such as plague, tularemia and tuberculosis. They are used to treat resistant infections caused by Gram‐negative bacilli

Streptomycin; gentamicin, kanamycin, amikacin.

Gram‐negative: Enterobacterales, Pseudomonas spp, Acinetobacter spp

Synergism with beta‐lactams and glycopeptides Enterococcus spp and S. aureus

Amphenicols (Am) inhibit bacterial protein synthesis. Very rarely used nowadays.

Chloramphenicol

Chloramphenicol is considered to have similar action to tetracycline (see below).

Other beta‐lactams: carbapenems (Ca) Carbapenems are beta‐lactams that have a broader spectrum of activity than most other beta‐lactam antibiotics.

Examples include Imipenem; meropenem; ertapenem; aztreonam.

Gram‐negative: including Extended‐sectrum betalactamase producing bacteria (ESBL+), H. influenzae e N. gonorrhoeae, Enterobacterales, Acinetobacter spp, P. aeruginosa
Gram‐positive: including Enterococcus faecalis, Listeria S. aureus

Anaerobes: including B. fragilis

Fluoroquinolones (F) target the bacterial DNA gyrase and topoisomerase. They are potent bacteriocidal agents against a broad variety of micro‐organisms.

Ciprofloxacin; levofloxacin; lomefloxacin; norfloxacin; sparfloxacin; clinafloxacin; gatifloxacin; ofloxacin; trovafloxacin, maxifloxacin.

Gram‐negative: Enterobacterales, Pseudomonas spp, Acinetobacter spp

Moxifloxacin and Levofloxacin: as above plus Streptococci

Lincosamides (L) are protein synthesis inhibitors which bind to the 50s subunit of bacterial ribosomes and inhibit early elongation of peptide chain by inhibiting transpeptidase reaction.

Lincomycin; clindamycin.

Gram‐positive aerobes and anaerobes, including S. Aureus and Streptococci, not Enterococci

Macrolides (M) inhibit bacterial protein synthesis. Resistance can arise.

Erythromycin; clarithromycin; azithromycin.

Streptococcus pneumoniae,S. aureus, Listeria monocytogenes, Neisseria spp, Chlamydia spp, Legionella spp, Haemophilus spp

Nitroimidazoles (N) Nitroimidazole is an imidazole derivative that contains a nitro group. It is used for the treatment of infection with anaerobic organisms.

Metronidazole; tinidazol.

Clostridium spp, Eubacterium spp, Peptococcus spp, Peptostreptococcus spp, Fusobacterium spp, Gardnerella, Mobiluncus, Trichomonas, Entamoeba spp

Tetracyclines (T) are bacteriostatic antibiotics active against a wide range of aerobes and anaerobic gram‐positive and gram‐negative bacteria. They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome.

Tetracyclines should not be used with children under 8 and specifically during teeth development as they can cause a permanent brown discolouration to the teeth. This antibiotic is, therefore, unlikely to be used at caesarean section.

Tetracycline; doxycycline; minocycline.

Staphylococcus aureus, Streptococcus pneumonia, Streptococcus pyogenes, Streptooccus agalacticae, Campylobacter jejuni, Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitides,Clostridium spp., Peptostreptococcus spp., Peptococcus spp. Bacteroides melaninogenicus, Bacteroides fragilis

This table was originally adapted from information at https://www.emedexpert.com/classes/antibiotics.shtml, and has been revised for the 2020 update (Drew 2020; Letourneau 2020a; Letourneau 2020b; Letourneau 2020c; Letourneau 2020d; WHO 2020.

Potential adverse effects of antibiotics

On the mother

The benefits of antibiotics are well‐known, but there are potential adverse effects which also need to be considered. Antibiotic use is associated with some gastrointestinal symptoms (nausea, vomiting or diarrhoea), skin rashes, thrush/candidiasis (infection with candida which can affect both mother and baby), and joint pain (Dancer 2004). Occasionally there can also be blood problems, or kidney or liver damage (Dancer 2004; Martinez de Tejada 2014; Seedat 2017), and very occasionally anaphylaxis (a hypersensitivity reaction leading to pallor, shock and collapse, which is sometimes fatal). Possible interactions with other drugs the mother may be taking also need to be considered.

On the infant

Some antibiotics can reach the baby during labour or through breastfeeding, and these may upset the pattern of friendly bacterial flora being established in the baby's gut as part of the baby's immune system (Bedford Russell 2006; Penders 2006). There is evidence that this impact can continue for up to six months after birth and the consequences of this may occasionally be late‐onset serious bacterial infections (Glasgow 2005). It has been proposed that perinatal exposure to certain agents can cause irreversible changes to health conditions in adulthood through impact on hormonal imprinting (Csaba 2007; Korpela 2018; Mueller 2015). It is also possible that babies born prematurely, with less mature immune systems, may be affected more (Madhok 2015). Tetracyclines are usually not recommended during pregnancy or childbirth (BNF 2020). The current evidence favours the administration of antibiotics 15 to 60 minutes before incision, which was recognised to be better for preventing maternal infections and with no proven harm on the baby when short‐term outcomes were assessed (Mackeen 2014). However, the possibility that antibiotic exposure may adversely effect the newborn's developing immune system and microbiome needs to be assessed by collection of longer‐term data. 

Drug‐resistant strains of bacteria

Resistance of bacteria to antibiotics is spreading, and develops when a strain of bacteria evolves ways to escape the effects of the antibiotics. The antibiotic kills the non‐resistant bacteria allowing the resistant ones to colonise and spread or pressures them into evolving resistance mechanisms. Widespread use of antibiotics can contribute to the development of drug‐resistant strains of bacteria, which means that these antibiotics become ineffective because of bacterial resistance (Dancer 2004). At a population level this is a critical problem which may cause an increase in serious morbidity from hospital‐acquired drug‐resistant infections (Dancer 2004). This drug resistance is unlikely to be detected in randomised controlled trials and other types of research are needed to assess the potential problem of drug‐resistant strains (e.g. MRSA (Methicillin‐resistant Staphylococcus aureus), C difficile) in hospitals. The dose and number of antibiotic administrations given are a major consideration in relation to antibiotic resistance. These issues will be addressed in the other research ‐ seeDifferences between protocol and review for details.

Why it is important to do this review

Since there are an overwhelming number of effective antibiotics available, attempts to define an antibiotic regimen of choice have been problematic. Ideally, such a drug regimen should be: (1) proven to be effective in well‐designed prospective, randomised, double‐blind clinical trials, (2) active against the majority of pathogens likely to be involved, (3) able to attain adequate serum and tissue levels throughout the procedure, (4) not associated with the development of antimicrobial resistance, (5) inexpensive, and (6) well‐tolerated. In many respects penicillins and cephalosporins meet these criteria. Many investigators have used these drugs and have recommended that drugs from these classes represent the antibiotics of choice for caesarean section prophylaxis (Lamont 2011; RCOG 2011; Skeith 2017). However, current knowledge of bacterial resistance may challenge these recommendations.

The past several decades have seen an increase in the incidence of caesarean section, associated with an increase in maternal postoperative infection. Studies indicate that wound infection can be as high as 30% and endometritis as high as 60% where prophylactic antibiotics have not been utilised (Hofmeyr 2010). Therefore, infectious complications that occur following caesarean section are an important contributor to maternal morbidity and mortality (Martin 2014; Pierson 2018). Such complications are also an important source of increased hospital stay and consumption of financial resources. Prophylactic antibiotics for caesarean section can be expected to result in a major reduction in postoperative infectious morbidity. The question that remains, therefore, is which regimen to use?  This review is an update of the review last published in 2014 (Gyte 2014).

Other Cochrane Reviews have addressed: effectiveness against placebo (Smaill 2014), different routes of administration (Nabhan 2016) and various timings of administration (Mackeen 2014). In addition, two other reviews are proposed on dosage by the various sub‐types of cephalosporins and pencillins (still to be undertaken).

Objectives

To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) where the intention was to allocate participants randomly to one of at least two alternative classes of regimens of antibiotic prophylaxis for caesarean section. We excluded quasi‐RCTs. Cluster‐RCTs were eligible for inclusion but none were identified. Cross‐over trials were not eligible for inclusion.

Types of participants

Women undergoing caesarean section, both elective and non‐elective.

Types of interventions

Prophylactic antibiotic regimens comparing different classes of antibiotics. We included studies where there was a comparison between two or more antibiotics from the different classes. We looked at antibiotics administered singly or in combination with antibiotics of other classes or in combination with other drugs. The different classes of antibiotics are described and categorised, and also given a shorthand code for ease of reference (e.g. C1 for first‐generation cephalosporins) in Table 1. Where we identified different drugs in the same class of antibiotics being studied, we pooled these data, with some exceptions described below.

The main causative agents of caesarean section infection are skin colonizers, primarily gram‐positive cocci (particularly including Staphylococcus aureus (S. aureus) and Streptococci); and vaginal colonizers, including anaerobes and, to a lesser extent, gram‐negative bacilli.

In the previous update of this review, the main comparison was between cephalosporins and penicillins. We have revised our main comparisons to reflect trends in global practice to include the following.

I. Antistaphylococcal (i.e. potentially active against S.aureus) cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides (especially clindamycin)

II. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides (especially clindamycin) plus aminoglycosides (especially gentamicin)

III. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus penicillins P2+ (broad spectrum penicillins plus betalactamase inhibitors)

As these comparisons indicate, for this update we have not pooled the data for all penicillins or for all cephalosporins, because of important variations in spectra of action between different sub‐classes (including different generations, sub‐types and co‐formulations) of both of these classes of drugs. Where sub‐classes of these drugs are known to differ in their potential to act against agents that are the principle causes of infection at caesarean section, we have meta‐analysed the results of trials of different sub‐classes separately. Where sub‐classes of drugs are known to have similar potential action against these agents, we have pooled the results.

In the case of penicillins, both natural penicillins (P1, also referred to as first‐generation penicillins) and broad spectrum penicillins (P2; encompassing second‐, third‐ and fourth‐generation penicillins), are not active against S. aureus. By contrast, broad spectrum penicillins plus betalactamase inhibitors (P2+; available as co‐formulations, or administered together), and antistaphylococcal penicillins (P3), and are potentially effective against S. aureus. The natural penicillins and broad spectrum penicillins do not differ substantially in their potential action against other relevant agents, therefore, we have pooled results for these drugs (P1 and P2). Although both are potentially active against S. aureus, we analysed each of broad spectrum penicillins plus betalactamase inhibitors (P2+) and antistaphylococcal penicillins (P3) separately, because the former have a much broader spectrum of activity than antistaphylococcal penicillins (including action against gram‐negative bacilli and anaerobes including Bacteroides fragilis). Interventions combining penicillins with other classes of antibiotics have not been pooled with findings for penicillins either alone or in combination with betalactamase inhibitors. For comparisons including penicillins, penicillins are analysed as the control drug.

In terms of cephalosporins, we have pooled the findings on first‐ and second‐generation drugs (C1 and C2) because both of these subclasses are potentially active against gram‐positive cocci. However, third‐generation cephalosporins (C3) have only minimal action against S. aureus, so results from trials where women were given any third‐generation drug have been analysed separately. We have analysed fourth‐generation cephalosporins (C4) separately, because they have a much broader spectrum of activity than the other three generations (including action against S. aureus, some gram‐negative bacilli, and potential action against Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii)). Cephalosporins co‐formulated with betalactamase inhibitors result in a broader spectrum especially regarding gram‐negative and anaerobes, and, therefore we have also analysed them separately. Interventions combining cephalosporins with other classes of antibiotics have not been pooled with findings for cephalosporins either alone or in combination with betalactamase inhibitors.
For both penicillins and cephalosporins, while we have pooled different subclasses of drugs due to similarities in potential action against agents that cause infection at caesarean section, we acknowledge that there are nevertheless other differences in the spectra of action between the different subclasses of drugs. So, whilst we have structured the meta‐analysis based on the hypothesis that these differences will have little clinical impact when used for prophylaxis at caesarean section, where sufficient data were available, we have analysed the pooled findings for subgroup differences in order to assess whether there were, in fact, differences between natural penicillins and broad spectrum penicillins, and between first‐ and second‐generation cephalosporins, for this problem.

We excluded comparisons of different drugs within the same class of antibiotics, because it is anticipated that these will be assessed in four other Cochrane Reviews. Two of these reviews are as yet unpublished.

  • Different regimens of penicillin antibiotic given to women routinely for preventing infection after caesarean section

  • Different regimens of cephalosporin antibiotic given to women routinely for preventing infection after caesarean section

Two published reviews assess the appropriate timing and route of administration of prophylactic antibiotics at caesarean section.

  • Timing of prophylactic antibiotics for preventing infectious morbidity in women undergoing caesarean section (Mackeen 2014)

  • Routes of administration for antibiotic given to women routinely for preventing infection after caesarean section (Nabhan 2016)

Comparisons included

For classification of antibiotics and a key to the letter codes used throughout this review see Table 1.

Main comparisons

I. Antistaphylococcal (i.e. potentially active against S.aureus) cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides (especially clindamycin)

II. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides (especially clindamycin) plus aminoglycosides (especially gentamicin)

III. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+

Additional comparisons

IV. Cephalosporins versus penicillins (all remaining comparisons within these classes), including comparisons of different types of cephalosporin versus different types of penicillin as described below.

  • Antistaphylococcal cephalosporins C1 and C2 (1st and/or 2nd generation cephalosporins); or

  • Minimally antistaphylococcal (i.e. minimally active against S.aureus) cephalosporins C3 (3rd generation cephalosporins); or

  • Cephalosporins potentially active against S. aureus, P. aeruginosa and A. baumannii C4 (4th generation cephalosporins); or

  • Cephalospoprins plus betalactamase inhibitors C+

versus

  • Non‐antistaphylococcal (i.e. inactive against S. aureus) penicillins P1 and P2 (natural and broad spectrum penicillins); or

  • Penicillins plus betalactamase inhibitors P2+; or

  • Antistaphylococcal penicillins P3

V. All other comparisons of a single class versus a single class of antibiotic

VI. Comparisons including regimens of mixed classes in one or both groups

Types of outcome measures

Primary outcomes
Maternal

  1. Maternal sepsis (suspected or proven)

  2. Maternal endometritis

Infant

  1. Infant sepsis (suspected or proven)

  2. Infant oral thrush

Secondary outcomes
Maternal

  1. Maternal fever (febrile morbidity)

  2. Maternal wound infection

  3. Maternal urinary tract infection

  4. Maternal thrush

  5. Maternal serious infectious complication (such as bacteraemia, septic shock, septic thrombophlebitis, necrotising fasciitis, or death attributed to infection)

  6. Maternal adverse effects (e.g. allergic reactions, nausea, vomiting, diarrhoea, skin rashes)

  7. Maternal length of hospital stay

  8. Maternal infections ‐ post‐hospital discharge to 30 days postoperatively (not pre‐specified in the protocol)

  9. Maternal readmissions (not pre‐specified in the protocol)

Infant

  1. Immediate adverse effects of antibiotics on the infant (unsettled, diarrhoea, rashes)

  2. Infant length of hospital stay

  3. Infant long‐term adverse effects (e.g. general health, frequency of visits to hospital)

  4. Infant's immune system development (using a validated scoring assessment)

Additional outcomes

  1. Costs

Search methods for identification of studies

The following search methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.

Electronic searches

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register by contacting their Information Specialist (2 December 2019).

The Register is a database containing over 25,000 reports of controlled trials in the field of pregnancy and childbirth. It represents over 30 years of searching. For full current search methods used to populate Pregnancy and Childbirth’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link.

Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is maintained by their Information Specialist and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

  2. weekly searches of MEDLINE (Ovid);

  3. weekly searches of Embase (Ovid);

  4. monthly searches of CINAHL (EBSCO);

  5. handsearches of 30 journals and the proceedings of major conferences;

  6. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Search results are screened by two people and the full text of all relevant trial reports identified through the searching activities described above is reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set that has been fully accounted for in the relevant review sections (Included studies; Excluded studies; Ongoing studies).

In addition, we searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (2 December 2019) using the search methods detailed in Appendix 1.

Searching other resources

We searched the reference lists at the end of papers for further studies.

We did not apply any language or date restrictions.

Data collection and analysis

For methods used in the previous version of this review, seeGyte 2014.

For this update, the following methods were used for assessing the 17 reports that were identified as a result of the updated search.

The following methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.

Selection of studies

Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We resolved any disagreement through discussion or, if required, we consulted the third review author.

Data extraction and management

We designed a form to extract data. For eligible studies, two review authors extracted the data using the agreed form. We resolved discrepancies through discussion or, if required, we consulted the third review author. Data were entered into Review Manager software (RevMan 2014) and checked for accuracy.

When information regarding any of the above was unclear, we planned to contact authors of the original reports to provide further details.

Assessment of risk of bias in included studies

Two review authors independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Any disagreement was resolved by discussion or by involving a third assessor.

(1) Random sequence generation (checking for possible selection bias)

We described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We assessed the method as:

  • low risk of bias (any truly random process, e.g. random number table; computer random number generator);

  • high risk of bias (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number);

  • unclear risk of bias.

(2) Allocation concealment (checking for possible selection bias)

We described for each included study the method used to conceal allocation to interventions prior to assignment and assessed whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We assessed the methods as:

  • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

  • high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth);

  • unclear risk of bias.

(3.1) Blinding of participants and personnel (checking for possible performance bias)

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding unlikely to affect results. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed the methods as:

  • low, high or unclear risk of bias for participants;

  • low, high or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias)

We described for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed methods used to blind outcome assessment as:

  • low, high or unclear risk of bias.

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

We described for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported, or could be supplied by the trial authors, we planned to re‐include missing data in the analyses which we undertook.

We assessed the methods as:

  • low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups);

  • high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received (> 20% attrition) from that assigned at randomisation);

  • unclear risk of bias.

(5) Selective reporting (checking for reporting bias)

We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We assessed the methods as:

  • low risk of bias (where it is clear that all of the study’s pre‐specified outcomes and all expected outcomes of interest to the review have been reported);

  • high risk of bias (where not all the study’s pre‐specified outcomes have been reported; one or more reported primary outcomes were not pre‐specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);

  • unclear risk of bias.

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above)

We described for each included study any important concerns we had about other possible sources of bias.

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Handbook (Higgins 2011). With reference to (1) to (6) above, we planned to assess the likely magnitude and direction of the bias and whether we considered it is likely to impact on the findings. In future updates, we will explore the impact of the level of bias through undertaking sensitivity analyses ‐ seeSensitivity analysis.

Measures of treatment effect

Dichotomous data

For dichotomous data, we presented results as summary risk ratio with 95% confidence intervals.

Continuous data

We used the mean difference if outcomes were measured in the same way between trials. We planned to use the standardised mean difference to combine trials that measured the same outcome, but used different methods.

Unit of analysis issues

Cluster‐randomised trials

Had we identified any cluster‐RCTs we would have included them in the analyses along with individually‐randomised trials, following the methods described in Higgins 2011 and the Handbook [Section 16.3.4 or 16.3.6] using an estimate of the intracluster correlation co‐efficient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. In future updates, if we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identify both cluster‐randomised trials and individually‐randomised trials, we plan to synthesise the relevant information. We will consider it reasonable to combine the results from both if there is little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely.

We will also acknowledge heterogeneity in the randomisation unit and perform a sensitivity subgroup analysis to investigate the effects of the randomisation unit.

Other unit of analysis issues

No special methods were used for trials with more than one treatment group.

Dealing with missing data

For included studies, levels of attrition were noted. In future updates, if more eligible studies are included, the impact of including studies with high levels of missing data in the overall assessment of treatment effect will be explored by using sensitivity analysis.

For all outcomes, analyses were carried out, as far as possible, on an intention‐to‐treat basis i.e. we attempted to include all participants randomised to each group in the analyses. The denominator for each outcome in each trial was the number randomised minus any participants whose outcomes were known to be missing.

Assessment of heterogeneity

We assessed statistical heterogeneity in each meta‐analysis using the Tau², I² and Chi² statistics. We regarded heterogeneity as substantial if the Tau² was greater than zero or the I² was greater than 30% and there was a low P value (less than 0.10) in the Chi² test for heterogeneity. Where we identified substantial heterogeneity (above 30%), we explored it by pre‐specified subgroup analysis.

Assessment of reporting biases

Had we found 10 or more studies in the meta‐analysis, we would have investigated reporting biases (such as publication bias) using funnel plots. We would have assessed funnel plot asymmetry visually. If asymmetry was suggested by a visual assessment, we explored possible reasons for this.

Data synthesis

We carried out statistical analysis using the Review Manager software (RevMan 2014). We used fixed‐effect meta‐analysis for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect: i.e. where trials were examining the same intervention, and the trials’ populations and methods were judged sufficiently similar.

Where there was clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials, or if substantial statistical heterogeneity was detected, we used random‐effects meta‐analysis to produce an overall summary, if an average treatment effect across trials was considered clinically meaningful. The random‐effects summary was treated as the average of the range of possible treatment effects and we discussed the clinical implications of treatment effects differing between trials. If the average treatment effect was not clinically meaningful, we did not combine trials. If we used random‐effects analyses, the results were presented as the average treatment effect with 95% confidence intervals, and the estimates of Tau² and I².

Subgroup analysis and investigation of heterogeneity

For the 2020 update, we planned to undertake subgroup analyses.

  1. By type of caesarean section. In the previous version of this review, type of surgery was differentiated by elective caesarean section versus non‐elective caesarean section versus mixed or not defined (rupture of membranes for more than six hours or the presence of labour was used to differentiate a non‐elective caesarean section from an elective procedure). For this update, we intended to revise these subgroup distinctions, and differentiate surgery by urgency according the Royal College of Obstetrics and Gynaecology definitions, category 1 versus category 2 and 3 versus category 4 versus mixed or not defined (RCOG 2011), due to the fact that other infection control measures are especially compromised in the most urgent situations. However, the information reported in the available trials was not specific enough to support investigation by urgency in line with these definitions, therefore we retained the previous categorisation as described. Although we have presented results from these subgroup analyses for ease of reference, for most comparisons, there were too few trials to make the results of subgroup analyses meaningful.

  2. By generation of cephalosporin. Where we combined results for 1st and 2nd generation cephalosporins, we included an exploratory subgroup analysis by generation of cephalosporin. While we have presented these subgroup analyses in order to enable readers to easily see the distribution of different generations of cephalosporins in the included trials, there were too few trials and subgroups were too imbalanced in size for findings from these analyses to either support or bring in to question our hypothesis that data from these trials should be pooled.

  3. By type of penicillin. Where we combined results for natural and broad spectrum penicillins, we included an exploratory subgroup analysis by generation of penicillins. As for cephalosporins, while we have presented these subgroup analyses in order to enable readers to easily see the distribution of different generations of penicillins in the included trials, there were too few trials and subgroups were too imbalanced in size for findings from these analyses to either support or bring in to question our hypothesis that data from these trials should be pooled.

Although the regimen of antibiotics varied between trials, we did not plan to undertake subgroup analysis by the number of doses given because this is better assessed in other reviews (Different regimens of penicillin antibiotic given to women routinely for preventing infection after caesarean section and Different regimens of cephalosporin antibiotic given to women routinely for preventing infection after caesarean section). Other reviews cover timing and routes of administration (Timing of prophylactic antibiotics for preventing infectious morbidity in women undergoing caesarean sectionMackeen 2014 and Routes of administration for antibiotic given to women routinely for preventing infection after caesarean sectionNabhan 2016).

We planned to assess subgroup differences by interaction tests (Deeks 2001) available within RevMan (RevMan 2014) and to report the results of subgroup analyses quoting the Chi² statistic and P value, and the interaction test I² value.

Sensitivity analysis

We planned to carry out sensitivity analysis to explore the effect of risk of bias for important outcomes in the review. Where there was a high risk of bias associated with a particular aspect of a study, for example, inadequate sequence generation and allocation concealment (Schultz 1995), we planned to explore this by sensitivity analysis (Higgins 2011). However, there were too few studies included in any analysis assessed as being at low risk of bias for any meaningful sensitivity analysis in this update.

Summary of findings and assessment of the certainty of the evidence

For this update the certainty of the evidence was assessed using the GRADE approach as outlined in the GRADE handbook. We planned to assess the certainty of the body of evidence relating to the following outcomes for the main comparisons of: 1st and 2nd generation cephalosporins versus lincosamides; 1st and 2nd generation cephalosporins versus lincosamides plus gentamycin; 1st and 2nd generation cephalosporins versus penicillins plus betalactamase inhibitors. However, no trials reported on the first two comparisons, therefore we assessed the certainty of the evidence relating to 1st and 2nd generation cephalosporins versus penicillins plus betalactamase inhibitors; these assessments are reported in summary of findings Table 1.

  1. Maternal sepsis

  2. Maternal endometritis

  3. Infant sepsis

  4. Infant oral thrush

  5. Maternal wound infection

  6. Maternal urinary tract infection

  7. Maternal composite adverse effects (e.g. allergic reactions; nausea, vomiting, diarrhoea, skin rashes)

We used the GRADEpro Guideline Development Tool to import data from Review Manager 5.3 (RevMan 2014) in order to create a ’Summary of findings’ table. We used the GRADE approach to provide a summary of the intervention effect alongside an assessment of our confidence in the effect estimate for each of the above outcomes. The GRADE approach uses five considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the certainty of the body of evidence for each outcome. The evidence was downgraded from 'high certainty' by one level for serious (or by two levels for very serious) limitations relating to each of these five considerations.

Results

Description of studies

Results of the search

See Figure 1

Figure 1
Study flow diagram.

Study flow diagram.

The classification of antibiotics is set out in Table 1.

We assessed 33 new trial reports and we also revisited the two trial reports that were awaiting classification in the previous version of the review. We included four new trials (four reports) (Alekwe 2008; Deng 2007; Rohan 2014; Rudge 2006) and excluded 13 new trials (24 reports) (Azizi 2014; El Aish 2018; Gideon 2016; Jalai 2019; Jayawardena 2019; Mihailovic 1989; Mokhtar 2019; Opoku 2007; Sivasankari 2015; Tita 2016; Vathana 2018; Wajsfeld 2019; Westen 2015). We also added two new reports to trials already included (Mivumbi 2014; Ziogos 2010), and added three new reports to two previously excluded studies (Ijarotimi 2013; Lyimo 2013). We have no studies awaiting further classification, and have two ongoing studies (Abdalmageed 2019; Karamali 2013).

In all, we have identified 170 reports for 150 studies. For a detailed description of studies seeCharacteristics of included studies, Characteristics of excluded studies; Characteristics of studies awaiting classification and Characteristics of ongoing studies.

Included studies

Overall, our searches identified 39 included studies of which 33 provided data in a format that could be included in this review (Ahmed 2004; Alekwe 2008; Benigno 1986; Bracero 1997; Busowski 2000; Chantharojwong 1993; Deng 2007; Faro 1990; Ford 1986; Gidiri 2014; Jyothi 2010; Kamilya 2012; Kayihura 2003; Koppel 1992; Lehapa 1999; Lewis 1990; Louie 1982; Lumbiganon 1994; Mansueto 1989; Mivumbi 2014; Mothilal 2013; Noyes 1998; Parulekar 2001; Rehu 1980; Rohan 2014; Rosaschino 1988; Rudge 2006; Saltzman 1985; Saltzman 1986; Shah 1998; Spinnato 2000; van der Linden 1993; Ziogos 2010). These studies included data on 8073 women. The six studies which did not provide data for the analyses were: four full‐text papers (Dashow 1986; Graham 1993; Ng 1992; Voto 1986); and two of the conference abstracts (De‐Lalla 1988; Wells 1994).

The studies were published between 1980 and 2014. Five studies were reported as conference abstracts only (De‐Lalla 1988; Lehapa 1999; Lumbiganon 1994; Rohan 2014; Wells 1994). In this update, we have not included the data from two trials from which data were previously included: because there was inconsistency in the denominators between tables in the paper for one report (Dashow 1986); and because there was inconsistency between the tables and the main text in the other (Ng 1992). In both cases, the trials took place too long ago to obtain clarification from the authors.

Two studies reported sponsorship by a drug company (Bracero 1997; van der Linden 1993). One study reported that the drugs were donated by a drug company (Ahmed 2004), and one study reported that the hospital sponsored the research (Ziogos 2010). None of the other studies reported on their source of funding.

Four studies reported they had no conflicts of interest relating to their study (Alekwe 2008; Gidiri 2014; Mivumbi 2014; Ziogos 2010). One study was unclear as the original paper was not written in English and we need to seek help to ascertain this information (Mansueto 1989). The rest of the studies did not report if there was any conflict of interest or not.

Of the 39 studies included in the review, 22 were conducted in high‐income countries, eight in upper‐middle income, seven in lower‐middle income and two in low‐income countries (see Characteristics of included studies).

Participants

Of the trials contributing data to our analyses, six trials included only women who were having elective caesarean sections (Ahmed 2004; Alekwe 2008; Deng 2007; Jyothi 2010; Rohan 2014; Shah 1998); 11 trials included only women having non‐elective caesarean sections (Chantharojwong 1993; Faro 1990; Kayihura 2003; Lehapa 1999; Louie 1982; Lumbiganon 1994; Mansueto 1989; Noyes 1998; Rehu 1980; Saltzman 1986; van der Linden 1993); eight trials included a mixture of elective and non‐elective (Benigno 1986; Gidiri 2014; Kamilya 2012; Lewis 1990; Mivumbi 2014; Mothilal 2013; Spinnato 2000; Ziogos 2010); and in the remaining eight trials the type of caesarean section was not clearly described (Bracero 1997; Busowski 2000; Ford 1986; Koppel 1992; Parulekar 2001; Rosaschino 1988; Rudge 2006; Saltzman 1985).

Interventions and comparators

The studies contributing data to our analyses included women who received the following specific drugs within each class, either singly or in combination with other classes (see Table 1 for more information on each category of drug):

Cephalosporins (C):

  • 1st generation cephalosporins (C1): cefalothin; cefazolin; cephradine

  • 2nd generation cephalosporins (C2): cefotetan; cefoxitin; cefuroxime

  • 3rd generation cephalosporins (C3): cefotaxime; cefotoxime; ceftriaxone; ceftizoxime

Penicillins (P):

  • Natural penicillins (P1): benzathine penicillin; benzyl penicillin; crystalline penicillin; procaine penicillin

  • Broad spectrum penicillins (P2): ampicillin; mezlocillin; piperacillin; ticarcillin

  • Penicillins plus betalactamase inhibitors (P2+): ampicillin plus sulbactam; co‐amoxyclav = amoxicillin plus clavulanic acid; ticarcillin plus clavulanic acid

  • Antistaphylococcal penicillins (P3): cloxacillin

Other beta‐lactams, carbapenems (Ca): imipenem

Aminoglycasides (A): gentamicin

Amphenicols (Am): chloramphenicol

Fluoroquinolones: ciproflaxin

Lincosamides (L): clindamycin

Macrolides (M): azithromycin; erythromycin

Nitroimadazoles (N): metronidazole

The specific drugs that women received are described alongside the results for each comparison in Effects of interventions.

Most trials administered prophylactic antibiotics after skin incision.  Of the trials contributing data to the analyses, only eight trials gave all women in both groups antibiotics prior to skin incision (administration continued postoperatively for groups given multiple doses), with timing described as: preoperative (Gidiri 2014; Rosaschino 1988); at induction of anaesthesia (Ahmed 2004; Rohan 2014; van der Linden 1993); 30 minutes prior to surgery (Mothilal 2013; Rehu 1980); and < 60 minutes before incision (Mivumbi 2014).  One further trial (Kayihura 2003), gave women in the intervention group antibiotics pre‐operatively, with all women in the control group receiving them postoperatively. Nineteen trials gave all women in both groups antibiotics at or just after cord clamping (Benigno 1986; Bracero 1997; Busowski 2000; Chantharojwong 1993; Deng 2007; Faro 1990; Ford 1986; Jyothi 2010; Kamilya 2012; Koppel 1992; Louie 1982; Lumbiganon 1994; Mansueto 1989; Noyes 1998; Saltzman 1985; Saltzman 1986; Shah 1998; Spinnato 2000; Ziogos 2010); three trials gave antibiotics just after cord clamping in the intervention group and postoperatively in the control (Alekwe 2008; Parulekar 2001; Rudge 2006). In one trial, timing of administration was not reported (Lehapa 1999). One further trial used intraoperative irrigation (Lewis 1990). 

Fifteen studies administered a single dose of antibiotic systemically in all groups, and in most trials administration was specified as intravenous (Bracero 1997; Busowski 2000; Faro 1990; Jyothi 2010; Kamilya 2012; Koppel 1992; Mivumbi 2014; Noyes 1998; Rehu 1980; Rosaschino 1988; Spinnato 2000; Ziogos 2010), although in others this was not explicitly described (Lumbiganon 1994; Mothilal 2013; Rohan 2014). Seven studies administered multiple doses systemically in all groups, intravenously (Benigno 1986; Chantharojwong 1993; Deng 2007; Lehapa 1999; Louie 1982), or route not explicitly described Ford 1986; Saltzman 1985). Ten two‐arm studies administered a single dose to one group and multiple doses to the other, all systemically but with the route of administration varying somewhat between trials. In four of these studies, all women received all antibiotics intravenously (Ahmed 2004; Mansueto 1989; Shah 1998; van der Linden 1993); Rudge 2006 administered a single dose of antibiotics intravenously (C1) versus multiple IM (P1); Alekwe 2008; Gidiri 2014; Kayihura 2003; Parulekar 2001 compared a single dose intravenous versus initial intravenous and then oral and Iintramuscular for remains of the course. In the remaining study, route was not explicitly described (Saltzman 1986). The final trial contributing data administered antibiotics via intraoperative irrigation in both groups rather than systemically (Lewis 1990). See Characteristics of included studies for detailed information on dose and regimen for each study.

Main comparisons (systemic administration)

See Table 2 for an overview of all the comparisons reported in the included studies.

Open in table viewer
Table 2. Comparison matrix

Intervention/comparison class
or sub‐class of
antibiotic

Single class administered

Multiple classes administered

Antistaphylococcal cephalosporins (C1 and C2; 1st and 2nd generation)

Minimally antistaphylococcal cephalosporins (C3; 3rd generation)

Broad spectrum penicillins plus betalactamase inhibitors (P2+)

Lincosamide (L) plus aminoglycoside (A)

Antistaphylococcal cephalosporins (C1 and C2; 1st and 2nd generation) plus nitroimadazole (N)

Aminoglycaside (A) plus nitroimidazole (N)

Minimally antistaphylococcal cephalosporins (C3; 3rd generation) plus nitroimidazole (N)

Single class administered

Broad spectrum penicillins plus betalactamase inhibitors (P2+)

8 trials
(1540 women)

2 trials
(865 women)

Comparison not within scope of review

No trials

1 trial

(83 women)

No trials

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum)

Systemic administration:
9 trials
(3093 women)

Lavage: 1 trial (383 women)

4 trials
(854 women)

Comparison not within scope of review

1 trial

(88 women)

1 trial

(139 women)

No trials

No trials

Broad spectrum penicillins (P2) and antistaphylococcal penicillins (P3)

No trials

1 trial
(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Fluoroquinolones (F)

1 trial

(81 women)

No trials

1 trial

(72 women)

No trials

No trials

No trials

No trials

Carbapenems (Ca)

No trials

1 trial

(48 women)

No trials

No trials

No trials

No trials

No trials

Macrolides (M)

1 trial

(70 women)

No trials

No trials

No trials

No trials

No trials

No trials

Multiple classes administered

Broad spectrum penicillin (P2) plus antistaphylococcal penicillin (P3) plus aminoglycoside (A) plus nitroimadazole (N)

No trials

1 trial

(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Antistaphylococcal penicillin (P3) plus aminoglycoside (A)

No trials

1 trial

(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Natural penicillin (P1) plus nitroimidazole (N) plus macrolide (M)

No trials

No trials

Comparison not within scope of review

No trials

No trials

1 trial
(241 women)

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum) plus nitroimadazole (N)

No trials

No trials

Comparison not within scope of review

No trials

2 trials
(256 women)

No trials

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum) plus nitroimadazole (N) plus amphenicol (Am)

No trials

No trials

Comparison not within scope of review

No trials

No trials

No trials

1 trial

(232 women)

We included three main comparisons.

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides

No included studies reported.

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides plus aminoglycosides

No included studies reported.

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors P2+

Eight trials, which provided data on 1540 women, reported on our third main comparison (Bracero 1997; Busowski 2000; Jyothi 2010; Lumbiganon 1994; Noyes 1998; Saltzman 1985; Spinnato 2000; Ziogos 2010).

Additional comparisons (systemic administration)
Cephalosporins versus penicillins (pre‐specified comparisons)

For this update, we did not pool data on all generations of cephalosporins, or all subtypes of penicillins. We combined data on cephalosporins potentially active against staphylococcus aureus (1st and 2nd generation cephalosporins, C1 and C2), and we also combined data on non‐antistaphylocccal penicillins (natural and broad spectrum penicillins) (further details of drugs, their spectra of action, and key to abbreviations (C1, P1 etc) are described in Table 1). We did not pool data on other subtypes of these two classes of drug. According to this pre‐specified comparison structure, which is described in our Methods, the included studies reported on the following comparisons.

Cephalosporins potentially active against S. aureus C1 and C2 (1st and 2nd generation) versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum)

Twelve trials included this comparison for systemic administration (Benigno 1986; Chantharojwong 1993; De‐Lalla 1988; Faro 1990; Ford 1986; Graham 1993; Louie 1982; Mivumbi 2014; Rudge 2006; Saltzman 1986; Spinnato 2000; Voto 1986).

Three out of the 12 trials (De‐Lalla 1988; Graham 1993; Voto 1986) did not contribute data to the analyses.

Cephalosporins with minimal action against S. aureus C3 (3rd generation) versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum)

Five trials included this comparison (Faro 1990; Lehapa 1999; Louie 1982; Ng 1992; Rosaschino 1988), however Ng 1992 did not contribute data to the analyses.

Cephalosporins with minimal action against S. aureus C3 (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors P2+

Two trials included this comparison (Kamilya 2012; Koppel 1992).

No included studies gave women either cephalosporins potentially active against S. aureus, P. aeruginosa and A. baumannii C4 (4th generation), or cephalosporins plus betalactamase inhibitors C+.

Other cephalosporin (only) regimens versus other penicillin (only) regimens

Cephalosporins C3 (3rd generation) versus penicillins P2 and P3 (broad spectrum and antistaphylococcal)

One study (Ahmed 2004) included this comparison.

All other comparisons of a single class versus a single class of antibiotic

Fluoroquinolones F versus broad spectrum penicillins plus betalactamase inhibitors P2+

One study (Busowski 2000) included this comparison.

Fluoroquinolones F versus cephalosporins C2 (2nd generation)

One study (Busowski 2000) included this comparison.

Carbapenems Ca versus cephalosporins C2 (2nd generation)

One study (Mansueto 1989) included this comparison.

Macrolides M versus cephalosporins C1 (1st generation)

One study (Mothilal 2013) included this comparison.

Other antibiotic regimens (multiple classes) versus cephalosporin (only) regimens

Two studies included comparisons of other antibiotic regimens (multiple classes) versus cephalosporin (only) regimens. The findings were not pooled because the regimens differed substantially between trials.

Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycoside A plus nitroimidazole N versus cephalosporin C3 (3rd generation)

One study (Alekwe 2008) included this comparison.

Antistaphylococcal penicillin P3 plus aminoglycoside A versus cephalosporin C3 (3rd generation)

One study (Parulekar 2001) included this comparison.

Other antibiotic regimens (multiple classes) versus penicillin (only) regimens

Three studies included comparisons of other antibiotic regimens (multiple classes) versus penicillin (only) regimens. The findings were not pooled because the regimens differed substantially between trials.

Lincosamide L plus aminoglycoside A versus natural penicillin P1

One study (Rehu 1980) included this comparison.

Cephalosporin C1 (1st generation) plus nitroimadazole versus broad spectrum penicillin P2

One study (Shah 1998) included this comparison.

Cephalosporin C2 (2nd generation) plus nitroimidazole N versus broad spectrum penicillin plus betalactamase inhibitors P2+

One study (van der Linden 1993) included this comparison.

Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes)

Four studies included comparisons of other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes). The findings were not pooled because the regimens differed substantially between trials.

Aminoglycoside A plus nitroimidazole N versus natural penicillin P1 plus nitroimidazole N plus macrolide M

One study (Kayihura 2003) included this comparison.

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) plus nitroimadazole N versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) nitroimadazole N

Two studies (Deng 2007; Rohan 2014) included this comparison.

Cephalosporin C3 (3rd generation) plus nitroimidazole N versus natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimidazole N plus amphenicol Am

One study (Gidiri 2014) included this comparison.

Additional comparisons (irrigation/lavage administration)

Two trials (Dashow 1986; Lewis 1990) administered antibiotics via lavage, rather than systemically, and for this update they were considered separately from the trials using systemic administration.

Cephalosporins potentially active against S. aureus C1 and C2 (1st and 2nd generation) versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum)

Both trials (Dashow 1986; Lewis 1990) reported on this comparison, however Dashow 1986 did not contribute data to the analyses.

Excluded studies

We excluded 109 studies for the following reasons.

(seeCharacteristics of excluded studies).

Risk of bias in included studies

See Figure 2 for a summary of 'Risk of bias' assessments. We followed the methods described in the Cochrane Handbook (Higgins 2011) when assessing included studies for risk of bias.

Figure 2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Allocation

We considered six studies to have adequate sequence generation and allocation concealment (Alekwe 2008; Benigno 1986; Bracero 1997; Dashow 1986; Mivumbi 2014; Ziogos 2010). We assessed five further studies as low risk of bias for sequence generation but for allocation concealment they were unclear (Faro 1990; Graham 1993; Kamilya 2012; Rudge 2006) or high risk (Deng 2007). The reports for the remaining 27 studies were unclear about how adequately investigators had addressed these aspects to minimise bias with one study being unclear on sequence generation and high risk of bias for allocation concealment (Gidiri 2014).

Blinding

We assessed 13 studies as low risk for performance bias (Benigno 1986; Bracero 1997; Busowski 2000; Dashow 1986; Kamilya 2012; Koppel 1992; Lehapa 1999; Lewis 1990; Louie 1982; Rehu 1980; Saltzman 1985; Saltzman 1986; Spinnato 2000), 11 as high risk (Ahmed 2004; Alekwe 2008; Deng 2007; Faro 1990; Gidiri 2014; Graham 1993; Kayihura 2003; Mivumbi 2014; Rudge 2006; Voto 1986; Ziogos 2010), and we found the remaining 15 to be at unclear risk of performance bias.

For detection bias, we assessed eight studies as low risk (Benigno 1986; Busowski 2000; Dashow 1986; Kamilya 2012; Koppel 1992; Louie 1982; Rehu 1980; Rudge 2006), two as high risk (Kayihura 2003; Ziogos 2010) and the remaining 29 studies as unclear risk.

Incomplete outcome data

We found 29 studies to be at low risk of attrition bias (Ahmed 2004; Alekwe 2008; Bracero 1997; Busowski 2000; Chantharojwong 1993; Deng 2007; Ford 1986; Gidiri 2014; Graham 1993; Jyothi 2010; Kamilya 2012; Kayihura 2003; Koppel 1992; Louie 1982; Lumbiganon 1994; Mansueto 1989; Mivumbi 2014; Mothilal 2013; Ng 1992; Noyes 1998; Parulekar 2001; Rehu 1980; Rohan 2014; Rosaschino 1988; Rudge 2006; Saltzman 1986; Spinnato 2000; van der Linden 1993; Ziogos 2010). We found two studies to be at high risk for attrition bias where there was greater than 20% attrition post‐randomisation and attrition was imbalanced between groups (Benigno 1986; Voto 1986); for Voto 1986 attrition was so imbalanced that we considered the groups to be improperly randomised and the data from this study was not included in the meta‐analysis. For eight studies we found the risk of attrition bias to be unclear (Dashow 1986; De‐Lalla 1988; Faro 1990; Lehapa 1999; Lewis 1990; Saltzman 1985; Shah 1998; Wells 1994).

Selective reporting

We assessed that none of the included studies were low risk for selective reporting bias but we found seven studies to be high risk (Ahmed 2004; De‐Lalla 1988; Deng 2007; Lewis 1990; Noyes 1998; Saltzman 1985; Wells 1994), with the remaining 32 studies unclear.

Other potential sources of bias

All the included studies were at unclear risk of other sources of bias; many of the studies were quite old and it was difficult to assess if there were other possible biases.

Effects of interventions

See: Summary of findings 1 Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section

Main comparisons (systemic administration)

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides

No included trials reported this comparison.

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus lincosamides plus aminoglycosides

No included trials reported this comparison.

Comparisons 1 to 3: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors P2+

Eight trials, which provided data on 1540 women reported on our third main comparison, 1st and 2nd generation cephalosporins C1 and C2 versus broad spectrum penicillins plus betalactamase inhibitors P2+ (Bracero 1997; Busowski 2000; Jyothi 2010; Lumbiganon 1994; Noyes 1998; Saltzman 1985; Spinnato 2000; Ziogos 2010).

The subtype of drugs that women received varied between trials (for ease of reference, see Table 3 for a detailed summary of drugs, doses and single/multiple dosing used in comparisons including more than two trials).

Open in table viewer
Table 3. Interventions: drugs and doses

Antistaphylococcal cephalosporins (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors

(8 trials, 1 540 women)

Antistaphylococcal cephalosporins (1st and 2nd generation)

vs

Broad spectrum penicillins plus betalactamase inhibitors

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefazolin

1 g single dose

289

Ampicillin plus sulbactam

1 g single dose

87

2 g single dose

67

1.5 g single dose

128

Cefotetan

1 g single dose

224

3 g single dose

192

2 g single dose

96

Co‐amoxyclav (amoxicillin plus clavulanic acid)

1.2 g single dose

188

Cefoxitin

2 g x 3 doses

68

2.4 g single dose

55

Cefuroxime

1.5 g single dose

85

Ticarcillin plus clavulanic acid

(3 g + 100 mg)
x 3 doses

61

Antistaphylococcal cephalosporins (1st and 2nd generation) vs non‐antistaphylococcal penicillins (natural and broad spectrum)

(9 trials, 3 093 women)

Antistaphylococcal cephalosporins (1st and 2nd generation)

vs

Non‐antistaphylococcal penicillins (natural and broad spectrum)

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefazolin

1 g single dose

283

Ampicillin

2 g single dose

315

2 g single dose

161

1 g x 3 doses

113

1 g x 3 doses

261

Benzathine penicillin; and

Procaine penicillin

(1 200 000 IU and

400 000 IU) x 5 doses

200

Cefonicid

1 g

147

Mezlocillin

4 g single dose

51

Cefotetan

2 g, single dose

244

2 g x 3 doses

51

Cefoxitin

1 g single dose

155

Piperacillin

4 g single dose

155

2 g single dose

162

2 g x 3 doses

268

2 g x 3 doses

278

4 g x 3 doses

49

Cephalothin

2 g single dose

200

Minimally antistaphylococcal cephalosporins (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors

(2 trials, 865 women)

Minimally antistaphylococcal cephalosporins (3rd generation)

vs

Broad spectrum penicillins plus betalactamase inhibitors

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefotaxime

1 g single dose

431

Co‐amoxyclav (amoxicillin plus clavulanic acid)

1.2 g single dose

434

Minimally antistaphylococcal cephalosporins (3rd generation) vs non‐antistaphylococcal penicillins (natural and broad spectrum)

(4 trials, 854 women)

Minimally antistaphylococcal cephalosporins (3rd generation)

vs

Non‐antistaphylococcal penicillins (natural and broad spectrum)

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefotaxime

1 g x 3

55

Ampicillin

2 g

148

Ceftizoxime

1 g

135

1 g x 3

59

Ceftriaxone

1 g

145

1 g x 1;
then 500mg x 4

125

Mezlocillin

2 g

32

Piperacillin

4 g

155

  • Two trials compared 1st generation cephalosporin (cefazolin) versus co‐amoxyclav (amoxicillin plus clavulanic acid) (Jyothi 2010; Lumbiganon 1994).

  • One further trial also included a cefazolin group, with the control receiving ampicillin plus sulbactam; this trial also included an additional intervention group who received 2nd generation cephalosporin (cefotetan); we pooled th the data from the two cephalosporin groups for the main analysis (Noyes 1998).

  • Three trials compared 2nd generation cephalosporin (cefotetan) versus ampicillin plus sulbactam (Bracero 1997; Busowski 2000; Spinnato 2000).

  • One trial compared 2nd generation cephalosporin (cefuroxime) versus ampicillin plus sulbactam (Ziogos 2010).

  • One trial compared 2nd generation cephalosporin (cefoxitin) versus ticarcillin plus clavulanic acid (Saltzman 1985).

Five of the trials were two‐arm (Bracero 1997; Jyothi 2010; Lumbiganon 1994; Saltzman 1985; Ziogos 2010) and the other three were three‐arm (as described above, the data for the two cephalosporin arms in Noyes 1998 were pooled in the main analysis; Busowski 2000 included a third group of women who received fluoroquinolone (ciprofloxacin) (see comparisons 14 and 15); Spinnato 2000 included a third group who received only broad spectrum penicillin (ampicillin) (see comparisons 4 to 7).

Seven of the trials administered a single dose of antibiotic in both groups (Bracero 1997; Busowski 2000; Jyothi 2010; Lumbiganon 1994; Noyes 1998; Spinnato 2000; Ziogos 2010), and the other trial (Saltzman 1985) administered multiple doses in both groups.

All studies had some limitations in their design. For selection bias, only two studies were assessed as low risk (for both sequence generation and allocation concealment) (Bracero 1997; Ziogos 2010), and the remainder of studies were at unclear risk. For blinding, only one study was assessed as low risk (both performance and detection) (Busowski 2000), and one study was assessed as high risk of both aspects of blinding (Ziogos 2010). Also for blinding, three further studies were assessed as low risk for performance bias but unclear risk for detection bias (Bracero 1997; Saltzman 1985; Spinnato 2000), and the remainder were assessed as unclear. For incomplete outcome data, all studies were assessed as low risk of bias except one study which was unclear (Saltzman 1985). All studies were assessed as unclear for selective reporting bias and other biases.

Primary outcomes

Maternal sepsis: only one small study reported 'bacteraemia', which we have reported under this outcome. One woman, in the intervention group had bacteraemia. When compared with broad spectrum penicillins plus betalactamase inhibitors, the effect of antistaphylococcal cephalosporins (1st and 2nd generation) on maternal sepsis is uncertain (risk ratio (RR) 2.37, 95% confidence interval (CI) 0.10 to 56.41, 1 study, 75 women; very low‐certainty evidence) (Analysis 1.1; summary of findings Table 1).

Maternal endometritis: there may be little or no difference between antistaphylococcal cephalosporins and broad spectrum penicillin plus betalactamase inhibitors in preventing endometritis, however the 95% confidence interval is also compatible with both an increase or decrease in risk with antistaphylococcal cephalosporins (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low‐certainty evidence) (Analysis 1.2; summary of findings Table 1).

No included studies reported on infant sepsis or infant oral thrush.

Subgroup analysis by type of caesarean section

For our primary outcomes, there were too few studies that defined the type of caesarean section for subgroup analyses to be meaningful (Analysis 2.1; Analysis 2.2).

Subgroup analysis by type of cephalosporin

Similarly by type of cephalosporin, only two trials (268 women) administered 1st generation cephalosporins while six (893 women) gave 2nd generation cephalosporins. There appeared to be no indication of a difference in effect by generation of cephalosporin, consistent with the hypothesis underpinning our Methods. However, due to the relatively small number of trials and this imbalanced distribution, these exploratory subgroup analyses could not be expected to detect real differences in effect (Analysis 3.1; Analysis 3.2).

Secondary outcomes

Maternal fever: RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low‐certainty evidence (Analysis 1.3).

When compared with and broad spectrum penicillin plus betalactamase inhibitors, the effects of antistaphylococcal cephalosporins on all other reported secondary outcomes were uncertain.

Maternal wound infection: RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women; very low‐certainty evidence (Analysis 1.4; summary of findings Table 1).

Maternal urinary tract infection: average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women, random effects; very low‐certainty evidence (Analysis 1.5; summary of findings Table 1). There was substantial statistical heterogeneity in these results (Tau² = 1.56; Chi² = 5.96, df = 2 (P = 0.05); I² = 66%). We could find no explanation for this heterogeneity. There were too few studies and women for planned subgroup analyses to suggest a plausible explanation.

Maternal composite adverse effects: RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women; very low‐certainty evidence (Analysis 1.6; summary of findings Table 1)

Maternal allergic reactions: no events, not estimable, 2 studies, 373 women (Analysis 1.7)

Maternal skin rash: RR 1.08, 95% CI 0.28 to 4.11, 3 studies, 591 women; very low‐certainty evidence (Analysis 1.8)

Costs: two trials provided some information relating to cost of treatment. However, possibly due to differences in the specific type of cephalosporin administered, context, and time, their findings do not converge on the same overarching conclusion for this comparison:

  • Busowski 2000 described the cost of each drug to the patient at the hospital where the trial took place. Considering drug cost alone, the cephalosporin was more expensive: USD 72.00 for cefotetan 1 g versus USD 51.00 for ampicillin‐sulbactam 1.5 g.

  • Ziogos 2010 described the cost of antibiotics per women, cefuroxime EUR 2.38 versus ampicillin‐sulbactam EUR 5.07, suggesting that in Greece this cephalosporin may be cheaper.

The included studies did not report on any of our other secondary outcomes: maternal: thrush, composite serious infectious complication,other adverse effects (nausea, vomiting, diarrhoea); length of hospital stay; infections (post‐hospital discharge to 30 days postoperatively), readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits), immune system development.

Other comparisons (systemic administration)

Comparisons 4 to 13: Cephalosporins versus penicillins (all remaining comparisons within these classes)
Comparisons 4 to 7: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum)

Twelve trials included this comparison for systemic administration (Benigno 1986; Chantharojwong 1993; De‐Lalla 1988; Faro 1990; Ford 1986; Graham 1993; Louie 1982; Mivumbi 2014; Rudge 2006; Saltzman 1986; Spinnato 2000; Voto 1986). Three out of the 12 trials (De‐Lalla 1988; Graham 1993; Voto 1986) did not contribute data to the analyses. A total of nine trials contributed data on 3093 women to this comparison, however many trials did not report our priority outcomes (Benigno 1986; Chantharojwong 1993; Faro 1990; Ford 1986; Louie 1982; Mivumbi 2014; Rudge 2006; Saltzman 1986; Spinnato 2000).

For trials that contributed data to the analyses, the antibiotics that women received varied between trials, for both generation of cephalosporin and type of penicillin (for ease of reference, see Table 3 for a detailed summary of drugs, doses and single/multiple dosing used in comparisons including more than two trials).

  • One trial compared 1st generation cephalosporin (cephalothin) versus natural penicillins (benzathine penicillin and procaine penicillin) (Rudge 2006).

  • Three trials compared 1st generation cephalosporin (cefazolin) versus broad spectrum penicillin (ampicillin) (Chantharojwong 1993; Louie 1982; Mivumbi 2014).

  • One 10‐arm trial compared 1st generation cephalosporin (cefazolin, various doses/regimens) or 2nd generation cephalosporins (cefonicid or cefotetan, or cefoxitin various doses/regimens) versus broad spectrum penicillins (ampicillin or piperacillin). The results for each group given any dose or regimen of 1st generation cephalosporin, any dose or regimen of 2nd generation cephalosporins, or any broad spectrum penicillin, were pooled in our analyses (Faro 1990).

  • Two trials compared 2nd generation cephalosporin (cefoxitin) versus broad spectrum penicillin (piperacillin) (Benigno 1986; Ford 1986).

  • One trial compared 2nd generation cephalosporin (cefoxitin) versus broad spectrum penicillin (mezlocillin) (Saltzman 1986).

  • One trial compared 2nd generation cephalosporin (cefotetan) versus broad spectrum penicillin (ampicillin) (Spinnato 2000).

Six of the trials contributing data were two‐arm (Benigno 1986; Chantharojwong 1993; Ford 1986; Mivumbi 2014; Rudge 2006; Saltzman 1986), and the other three had multiple arms (Faro 1990; Louie 1982; Spinnato 2000). The results for different groups in Faro 1990 were combined as described above, and there was also another group who received 3rd generation cephalosporin ceftizoxime (see comparisons 8 to 10); Louie 1982 included a third group who received 3rd generation cephalosporin cefotaxime (see comparisons 8 to 10); Spinnato 2000 also a included a group who received penicillin plus betalactamase inhibitor (ampicillin plus sulbactam) (see comparisons 1 to 3).

Two trials administered women with a single dose of antibiotic in both groups (Mivumbi 2014; Spinnato 2000); one trial compared a single or multiple dose of antistaphylococcal cephalosporin versus a single dose of broad spectrum penicillin (Faro 1990); one trial compared multiple doses of antistaphylococcal cephalosporin versus a single or a multiple dose of broad spectrum penicillin (Saltzman 1986); one trial compared a single dose of cephalosporin versus multiple doses of penicillin (Rudge 2006); and the remaining four trials gave multiple doses of antibiotics to women in both groups (Benigno 1986; Chantharojwong 1993; Ford 1986; Louie 1982).

Of the nine studies contributing data to the analyses, all of them had some limitations in study design that could have biased the results. Only two studies were at low risk of selection bias for both sequence generation and allocation concealment (Benigno 1986; Mivumbi 2014), and all the others were at unclear risk for at least one or both sequence generation domains. Two studies reported blinding of participants, personnel and outcome assessors (Benigno 1986; Louie 1982), while three studies were at high risk of bias due to lack of blinding of participants and/or personnel (Faro 1990; Mivumbi 2014; Rudge 2006); and although the others were not at high risk of bias, they were at unclear risk for at least one blinding domain. One study was at high risk of bias due to incomplete outcome data (Benigno 1986), and all the other were at low risk. All studies were at unclear risk of bias due to selective reporting and other possible sources of bias.

Primary outcomes

Maternal endometritis: average RR 0.91, 95% CI 0.49 to 1.66, 6 studies, 2147 women, random effects (Analysis 4.1).

There was substantial statistical heterogeneity in the results for maternal endometritis (Tau² = 0.21; Chi² = 8.37, df = 5 (P = 0.14); I² = 40%). In line with our Methods, we, therefore, analysed the results using a random‐effects analysis. We note that the central effect estimate differs in direction when a fixed‐effect analysis is used (RR 1.15, 95% CI 0.86 to 1.56; Analysis 4.2), and the 95% CI shifts slightly although in both cases the CI is wide and does not clearly suggest a difference between interventions. Analysis using random effects gives more weight to small studies, and one smaller study Mivumbi 2014 reporting this outcome presented results that differed from other small studies, appearing to more clearly favour antistaphylococcal cephalosporins (cefazolin).

The observed statistical heterogeneity was not explained by our pre‐specified subgroup analyses (see below). Further sensitivity analysis suggested that it was due to this outlying result from Mivumbi 2014, where there were a relatively large number of events in the penicillin group. The study authors did acknowledge some important limitations in this study themselves, including a lack of performance blinding, which may have contributed to the divergent results (as may the fact that all other studies had design limitations). It is also possible that timing of administration may have been a contributing factor. Mivumbi 2014 was the only study that gave antibiotics before skin incision (the authors describe timing of administration as 'no more than 60 minutes prior to skin incision'), whereas all other studies contributing data gave antibiotics at or after cord clamping. Although this hypothesis aligns with the findings of Mackeen 2014, and we did not identify other differences that would account for Mivumbi 2014's outlying results, further investigation would be required to confirm whether timing of administration is, in fact, an explanatory factor.

Maternal sepsis, infant sepsis, and infant oral thrush were not reported by any included trials.

Subgroup analysis by type of caesarean section

For the only primary outcome where we have data (maternal endometritis), no included studies reported data on only women giving birth by elective caesarean section, while four studies included only women having non‐elective caesarean section, and the remaining two included a mixture of women having elective and non‐elective caesarean section but did not provide data on separate subgroups (Analysis 5.1).

Subgroup analyses by generation of cephalosporin and type of penicillin

Subgroup analyses by generation of cephalosporin (C1 versus C2) did not indicate different effects by these subtypes of drug (Chi² = 0.22, df = 1 (P = 0.64), I² = 0%; Analysis 6.1). All included studies reporting on this primary outcome only administered broad spectrum penicillins (P2) (Analysis 7.1).

Secondary outcomes

Maternal fever (febrile morbidity): average RR 0.74, 95% CI 0.39 to 1.41, 5 studies, 798 women, random effects (Analysis 4.3). There was substantial statistical heterogeneity in this result (Tau² = 0.28; Chi² = 8.66, df = 4 (P = 0.07); I² = 54%). Our planned subgroup analyses by type of caesarean section did not suggest an explanation (there were only five studies so any subgroup analysis will have limited validity; women underwent non‐elective caesarean section in two studies and mixed type of caesarean section in the other three), and nor did subgroup analysis by type of penicillin (all women received broad spectrum penicillins P2). It is possible that the administration of different generations of cephalosporin may have been a factor, with 1st generation cephalosporins potentially being more effective (Analysis 4.4; test for subgroup differences: Chi² = 4.65, df = 1 (P = 0.03), I² = 78.5%)). However, these results should be interpreted with caution given the small number of trials. Alternatively ‐ and similar to our results for endometritis ‐ sensitivity analysis suggested that this heterogeneity could be explained by outlying results in Mivumbi 2014: in which case, and as for endometritis above, it is possible that timing of administration may explain these differences (Mivumbi 2014 is the only trial that administered antibiotics pre‐operatively), however, this hypothesis would need to be confirmed by further investigation.

Maternal wound infection: RR 1.15, 95% CI 0.59 to 2.26, 5 studies, 915 women (Analysis 4.5).

Maternal urinary tract infection: average RR 1.36, 95% CI 0.59 to 3.14, 4 studies, 515 women, random effects (Analysis 4.6). There was again evidence of statistical heterogeneity in this result (Tau² = 0.15; Chi² = 3.70, df = 3 (P = 0.30); I² = 19%), which appeared to be explained by outlying results in Mivumbi 2014. It was not possible to assess whether this heterogeneity could be explained by our planned subgroup analyses (there were only four studies; all women had either non‐elective or mixed caesarean section; only one study out of four gave 2nd generation cephalosporins; all studies gave broad spectrum penicillins P2). As for endometritis and maternal fever above, sensitivity analysis suggested that it is possible that timing of administration may explain these differences (Mivumbi 2014 is the only trial that administered antibiotics pre‐operatively), however this hypothesis would need to be confirmed by further investigation.

Maternal composite adverse effects: RR 2.02, 95% CI 0.18 to 21.96, 2 studies, 1698 women (Analysis 4.7).

Maternal allergic reactions: no events, not estimable, 2 studies, 329 women (Analysis 4.8).

Maternal length of hospital stay: mean difference (MD) 1.5 days fewer, 95% CI 2.46 days fewer to 0.54 days fewer, 1 study, 132 women; (Analysis 4.9).

Costs: while most studies did not report this outcome, those that did provide information relating to cost of treatment calculated this in different ways (therefore, we have not meta‐analysed these data).

  • Ford 1986 reported the 'cost of prophylactic failure' in caesarean section, making an estimate of this cost based on many factors including hospital room, laboratory tests and fees, cost of drugs, pharmacy preparation and intravenous equipment; and possibly also psychological costs and clinician time although this was not entirely clear from the report (no breakdown of calculation given). The authors estimated the minimum cost of failure per 100 women to be cefoxitin USD 79, 074 versus piperacillin USD 26, 358, and argued that use of piperacillin for prophylaxis at caesarean section could realise significant cost savings. However, we note that these data relate to historic costs and may be out of date.

  • Louie 1982 reported a total figure per woman combining antibiotic costs and hospitalisation costs (which was calculated based on mean duration of hospitalisation of all successes and failures). Total costs per woman were: cefazolin CAD 1870.75 versus ampicillin CAD 2011.85, suggesting by contrast that the cephalosporin may be more cost‐effective. However, we note that these data relate to historic costs and may be out of date.

  • Rudge 2006 reported brief information on the unit cost of each drug in Brazil per woman, cephalothin USD 1.00 versus penicillins (benzathine penicillin and procaine penicillin) USD 1.17, suggesting the cephalosporin may be very slightly cheaper.

The included studies did not report on any of our other secondary outcomes: maternal: thrush, composite serious infectious complication, other adverse effects (nausea, vomiting, diarrhoea, skin rash),infections (post‐hospital discharge to 30 days postoperatively),readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparisons 8 to 10: Minimally antistaphylococcal cephalosporins C3 (3rd generation) versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum)

Five trials included this comparison (Faro 1990; Lehapa 1999; Louie 1982; Ng 1992; Rosaschino 1988), however, Ng 1992 did not contribute data to the analyses. Four trials contributed data on 854 women to our analyses (Faro 1990; Lehapa 1999; Louie 1982; Rosaschino 1988).

Of the four trials that contributed data to our analyses, all trials compared 3rd generation cephalosporins C3 versus broad spectrum penicillins P2, however, the specific drugs used varied (for ease of reference, see Table 3 for a detailed summary of drugs, doses and single/multiple dosing used in comparisons including more than two trials).

  • One trial compared cefotaxime versus ampicillin (Louie 1982)

  • One trial compared ceftriaxone versus ampicillin (Lehapa 1999)

  • One trial compared ceftriaxone versus mezlocillin (Rosaschino 1988)

  • One trial compared ceftizoxime versus piperacillin or ampicillin (Faro 1990)

Lehapa 1999 and Rosaschino 1988 were two‐arm trials. Faro 1990 included 10 arms (see also comparisons 4 to 7), and in our analysis a single C3 arm was compared with combined results for two groups (one piperacillin, one ampicillin). Louie 1982 included three arms, but the third arm received C1 (see comparisons 4 to 7).

Two trials administered a single dose of the antibiotic to women in each group (Faro 1990; Rosaschino 1988), and the other two trials gave multiple dose to women in both groups (Lehapa 1999; Louie 1982).

All four of the studies contributing data to the analyses had limitations in study design that could have biased the results. Only one study reported reliable random sequence generation (Faro 1990), but for this study it was unclear whether the allocation was adequately concealed; and all three other studies were at unclear risk of bias for both selection bias domains. Blinding was patchy across the studies, with only one study reporting complete blinding (Louie 1982), and one study assessed at high risk of bias due to lack of blinding of participants and personnel (Faro 1990); the two other studies at unclear risk of bias due to lack of blinding for one or both domains. Two studies presented no concerns regarding incomplete outcome data (Louie 1982; Rosaschino 1988), while the other two were assessed to be at unclear risk for this domain. All studies were at unclear risk of selective reporting bias and other possible sources of bias.

Primary outcomes

Maternal sepsis: no events, not estimable, 1 study, 59 women (Analysis 8.1).

Maternal endometritis: RR 1.74, 95% CI 1.10 to 2.75, 2 studies, 562 women (Analysis 8.2).

Infant sepsis andinfant oral thrush were not reported in any included trials.

Subgroup analyses by type of caesarean section and type of penicillin

For each of our primary outcomes where data were reported, all had the same type of caesarean section for any given outcome (Analysis 9.1; Analysis 9.2) and all women were administered broad spectrum penicillin P2 in all trials (Analysis 10.1; Analysis 10.2).

Secondary outcomes

Maternal fever (febrile morbidity): RR 0.89, 95% CI 0.29 to 2.76, 1 study, 114 women (Analysis 8.3).

Maternal wound infection: RR 0.41, 95% CI 0.13 to 1.28, 3 studies, 406 women (Analysis 8.4).

Maternal urinary tract infection: RR 0.54, 95% CI 0.05 to 5.75, 2 studies, 173 women (Analysis 8.5).

Maternal composite serious infectious complication: no events, not estimable, 1 study, 59 women (Analysis 8.6).

Maternal composite adverse effects: no events, not estimable, 2 studies, 507 women (Analysis 8.7).

Maternal allergic reactions: no events, not estimable, 1 study, 59 women (Analysis 8.8).

Maternal nausea: no events, not estimable, 1 study, 59 women (Analysis 8.9).

Materanl vomiting: no events, not estimable, 1 study, 59 women (Analysis 8.10).

Maternal diarrhoea: no events, not estimable, 1 study, 59 women (Analysis 8.11).

Maternal skin rash: no events, not estimable, 1 study, 59 women (Analysis 8.12).

Costs:

  • Louie 1982 reported a total figure per woman combining antibiotic costs and hospitalisation costs (which was calculated based on mean duration of hospitalisation of all successes and failures). Total costs per woman were: cefotaxime CAD 1764.50 versus ampicillin CAD 2011.85, suggesting that the cephalosporin may be more cost‐effective. However, we note that these data are historic and may not reflect contemporary prices.

  • Lehapa 1999 made a brief comment on costs, stating that quote: "[c]eftriaxone was associated with lower management costs. This being attributable to its once daily dosage and less hospital stay for those who received this antibiotic. The net saving in cost by using ceftriaxone instead of ampicillin was [ZAR]883.54 per patient." Although the authors suggest that again that the cephalosporin may be more cost‐effective, the saving is hard to interpret in the absence on absolute costs for each group or details of how it was calculated.

The included studies did not report on any of our other secondary outcomes: maternal: thrush; infant: immediate adverse effects infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; and costs).

Comparisons 11 and 12: Minimally antistaphylococcal cephalosporins C3 (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors P2+

Two trials reporting data on 865 women included this comparison (Kamilya 2012; Koppel 1992). Both studies compared cefotaxime versus co‐amoxyclav (amoxicillin plus clavulanic acid), and in both trials all women received a single dose.

Both studies appeared to have some limitations in study design that may have biased the results. While Kamilya 2012 reported adequate random sequence generation, this study was at unclear risk of bias for allocation concealment; and Koppel 1992 was at unclear risk of bias for both selection domains. Both studies reported complete blinding and no attrition, however, it was unclear whether there was a risk of bias due to selective reporting or any other possible sources of bias.

Primary outcomes

Maternal endometritis: RR 1.02, 95% CI 0.07 to 15.88, 2 studies, 865 women (Analysis 11.1).

The included studies did not report on our other primary outcomes, maternal sepsis, infant sepsis, and infant oral thrush.

Subgroup analysis by type of caesarean section

Data were only reported for one primary outcome (maternal endometritis), however the type of caesarean section that women underwent was either mixed (Kamilya 2012) or unclear (Koppel 1992) (Analysis 12.1).

Secondary outcomes

Maternal fever (febrile morbidity): RR 1.18, 95% CI 0.63 to 2.22, 1 study, 746 women (Analysis 11.2).

Maternal wound infection: average RR 0.67, 95% CI 0.10 to 4.58, 2 studies, 865 women, random effects (Analysis 11.3). There was moderate statistical heterogeneity in this result (Tau² = 1.14; Chi² = 1.93, df = 1 (P = 0.16); I² = 48%). With only two studies included, it was not possible to assess whether type of caesarean section could have been a factor here (moreover, Kamilya 2012 included mixed caesarean section and in Koppel 1992 type of caesarean section was unclear). We did not identify any other likely explanation for the observed variation in effects.

Maternal urinary tract infection: RR 0.51, 95% CI 0.05 to 5.46, 2 studies, 865 women (Analysis 11.4).

Maternal composite serious infectious complication: no events, not estimable, 1 study, 746 women (Analysis 11.5).

Maternal composite adverse effects: no events, not estimable, 2 studies, 865 women (Analysis 11.6).

Maternal allergic reactions: no events, not estimable, 2 studies, 865 women (Analysis 11.7).

Maternal nausea: no events, not estimable, 1 study, 119 women (Analysis 11.8).

Maternal vomiting: no events, not estimable, 1 study, 119 women (Analysis 11.9).

Maternal diarrhoea: no events, not estimable, 1 study, 119 women (Analysis 11.10).

Maternal skin rash: no events, not estimable, 1 study, 119 women (Analysis 11.11).

Maternal length of hospital stay: MD 0.01 shorter; 95% CI 0.12 shorter to 0.10 longer, 1 study, 746 women; unit assumed to be days given reported quantities although this is not explicit in trial report (Analysis 11.12).

The included studies did not report on any of our other secondary outcomes: maternal: thrush, infections (post‐hospital discharge to 30 days postoperatively),readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Comparison 13: Other cephalosporin (only) regimens versus other penicillin (only) regimens

One study reporting on 200 women (Ahmed 2004) compared cephalosporins C3 (3rd generation) versus penicillins P2 and P3 (broad spectrum and antistaphylococcal) (comparison 13, subgroup 1). All women received a single dose of ceftriaxone C3 versus multiple doses of ampicillin P2 plus cloxacillin P3. All women had elective caesarean sections.

Primary outcomes

Maternal endometritis: RR 2.00, 95% CI 0.18, to 21.71, 1 study, 200 women (Analysis 13.1).

This study did not report on our other primary outcomes (maternal endometritis, infant sepsis, and infant oral thrush).

Secondary outcomes

Maternal fever (febrile morbidity): RR 1.17, 95% CI 0.41 to 3.35, 1 study, 200 women (Analysis 13.2).

Maternal wound infection: RR 0.50, 95% CI 0.05 to 5.43, 1 study, 200 women (Analysis 13.3).

Maternal vomiting: RR 7.00, 95% CI 0.37 to 133.78, 1 study, 200 women (Analysis 13.4).

Maternal skin rash: RR 3.00, 95% CI 0.12 to 72.77, 1 study, 200 women (Analysis 13.5).

This study did not report on any of our other secondary outcomes: maternal: urinary tract infection, thrush; composite serious infectious complication, composite adverse effects;allergic reactions;nausea;diarrhoea;length of hospital stay; infant: immediate adverse effects;unsettled;diarrhoea;skin rash;length of hospital stay;general health;frequency of hospital visits and costs.

Other comparisons of single class versus single class of antibiotic (comparisons 14 to 17)

Three studies (Busowski 2000; Mansueto 1989; Mothilal 2013) included four different comparisons of single classes of antibiotics with one another.

Comparison 14: Fluoroquinolones F versus penicillins plus betalactamase inhibitors P2+

A three‐arm trial, Busowski 2000, compared ciproflaxin F versus ampicillin plus sulbactam P2+, with a total of 72 women contributing data to this analysis. All women received a single dose of antibiotic, and the type of caesarean section was unclear. This study was of questionable quality as it provided no information on sequence generation or allocation concealment, although there were no concerns of risk of bias due to lack of blinding or attrition.

Primary outcomes

Maternal sepsis: RR 2.55, 95 CI 0.11 to 60.57, 1 study, 72 women (Analysis 14.1).

Maternal endometritis: RR 1.17, 95% CI 0.68 to 2.01, 1 study, 72 women; (Analysis 14.2).

Infant sepsis and infant oral thrush were not reported.

Secondary outcomes

Maternal wound infection: RR 4.25, 95% CI 0.21 to 85.51; 1 study, 72 women (Analysis 14.3).

Maternal urinary tract infection: RR 0.09, 95% CI 0.01 to 1.69, 1 study, 72 women (Analysis 14.4).

Costs: this study described the cost of each drug to the patient at the hospital where the trial took place. Considering drug cost alone, the fluroquinolone was more expensive: USD 78.00 for ciproflaxin 200 mg versus USD 51.00 for ampicillin‐sulbactam 1.5 g.

This study did not report any of our other secondary outcomes: maternal: fever,serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes, thrush), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development).

Comparison 15: Fluoroquinolones F versus cephalosporins C2 (2nd generation)

Busowski 2000 also compared ciproflaxin F versus cefotetan C2. All women received a single dose of antibiotic, and the type of caesarean section was unclear. This study was of questionable quality as it provided no information on the sequence generation or allocation concealment, although there were no concerns of risk of bias due to lack of blinding or attrition.

Primary outcomes

Maternal sepsis: RR 1.08, 95% CI 0.07 to 16.63, 1 study, 81 women (Analysis 15.1).

Maternal endometritis: RR 1.29, 95% CI 0.76 to 2.19, 1 study, 81 women (Analysis 15.2).

Infant sepsis and infant oral thrush were not reported.

Secondary outcomes

Maternal wound infection: RR 2.15, 95% CI 0.20 to 22.82, 1 study, 81 women (Analysis 15.3).

Maternal urinary tract infection: no events, not estimable, 1 study, 81 women (Analysis 15.4).

Costs: this study described the cost of each drug to the patient at the hospital where the trial took place. Considering drug cost alone, the fluroquinolone was more expensive: USD 78.00 for ciproflaxin 200 mg versus USD 72.00 for cefotetan 1 g.

This study did not report any of our other secondary outcomes: maternal: fever,thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparison 16: Carbapenems versus cephalosporins C3 (3rd generation)

One trial reporting on 48 women (Mansueto 1989) compared a single dose of imipenem Ca versus multiple doses of cefotaxime C3. All women had non‐elective caesarean section. There was little information in the trial report and, therefore, this study was at unclear risk of bias for most domains, although there appeared to be no attrition.

Primary outcomes

Maternal endometritis: RR 1.18, 95% CI 0.08 to 17.82, 1 study, 48 women (Analysis 16.1).

Maternal sepsis, infant sepsis and infant oral thrush were not reported.

Secondary outcomes

Maternal fever (febrile morbidity): RR 0.59, 95% CI 0.06 to 6.09, 1 study, 48 women (Analysis 16.2).

Maternal wound infection: RR 0.39, 95% CI 0.02 to 9.15, 1 study, 48 women (Analysis 16.3).

Maternal urinary tract infection: no events, not estimable, 1 study, 48 women (Analysis 16.4).

This study did not report any of our other secondary outcomes: maternal: thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Comparison 17: Macrolides versus cephalosporins C1 (1st generation)

One small study reporting on 70 women (Mothilal 2013) compared azithromycin M versus cefazolin C1. All women received a single dose of antibiotic. There was little information in the trial report and, therefore, this study was at unclear risk of bias for most domains, although there appeared to be no attrition.

Primary outcomes

This study did not report any of our primary outcomes: Maternal sepsis andendometritis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 7.00, 95% CI 0.37 to 130.69, 1 study, 70 women (Analysis 17.1).

This study did not report any of our other secondary outcomes: maternal: wound infection, urinary tract infection, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Comparisons of other antibiotic regimens of multiple classes versus cephalosporins only (comparison 18)

For ease of reference, all trials making comparisons that fall within this category have been presented under a single comparison in our Data and analyses, however the data have not been totaled because the interventions and comparators varied substantially between trials.

Comparison 18 (subgroup 1): Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycoside A plus nitroimidazole N versus cephalosporin C3 (3rd generation)

One study reporting data for 200 women (Alekwe 2008) compared multiple doses of ampicillin P2 plus cloxacillin P3 plus gentamicin A plus metronidazole N versus a single dose of ceftriaxone C3. All women had elective caesarean section. This study was at low risk of selection bias, but high risk for performance blinding, and unclear risk for detection bias. There appeared to be no attrition, while it was unclear whether there was risk of bias due to selective reporting or other possible sources of bias.

Primary outcomes

Maternal endometritis: RR 1.07, 95% CI 0.55 to 2.10, 1 study, 200 women (Analysis 18.1).

This study did not report our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 0.86, 95% CI 0.30 to 2.46, 1 study, 200 women (Analysis 18.2).

Maternal wound infection: RR 1.14, 95% CI 0.43 to 3.03, 1 study, 200 women (Analysis 18.3).

Maternal urinary tract infection: RR 1.36, 95% CI 0.66 to 2.82, 1 study, 200 women (Analysis 18.4).

Maternal length of hospital stay: MD 0.11 days shorter, 95% CI 0.37 days shorter to 0.15 days longer, 1 study, 200 women (Analysis 18.5).

Costs: MD 5.98 US dollars (USD) higher, 95% CI 4.28 USD higher to 7.68 USD higher, 1 study, 200 women (Analysis 18.6).

This study did not report any of our other secondary outcomes: maternal:thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparison 18 (subgroup 2): Antistaphylococcal penicillin P3 plus aminoglycaside A versus cephalosporin C3 (3rd generation)

One study including 200 women (Parulekar 2001) compared multiple doses of cloxacillin P3 plus gentamicin A versus a single dose of cefotaxime C3. The type of caesarean section was unclear. There was little information in the trial report and, therefore, this study was at unclear risk of bias for most domains, although there appeared to be no attrition.

Primary outcomes

Maternal endometritis: RR 17.00, 95% CI 0.99 to 290.62, 1 study, 200 women (Analysis 18.1).

This study did not report our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 8.00, 95% CI 1.89 to 33.89, 1 study, 200 women (Analysis 18.2).

Costs: this trial reported the total cost of drugs and syringes per woman in each group as Indian rupees (INR) 320 versus INR 106, suggesting that a singe dose of C3 may be cheaper than the combined cost of multiple doses of the mixed regimen.

This study did not report any of our other secondary outcomes: maternal:wound infection, urinary tract infection, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparisons of other antibiotic regimens of multiple classes versus penicillins only (comparison 19)

For ease of reference, all trials making comparisons that fall within this category have been presented under a single comparison, however the data have not been totaled because the interventions and comparators varied substantially between trials.

Comparison 19 (subgroup 1): Lincosamide plus aminoglycoside versus natural penicillin P1

One trial compared single doses of clindamycin L plus gentamicin A versus a single dose infusion of benzyl penicillin P1 (Rehu 1980). All women had non‐elective caesarean sections. This study was at unclear risk of selection bias, but low risk of bias for blinding and attrition. It was at unclear risk of selective reporting or other bias.

Primary outcomes

Maternal endometritis: RR 1.46, 95% CI 0.35 to 6.15, 1 study, 88 women (Analysis 19.1).

This study did not report our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal wound infection: RR 1.10, 95% CI 0.16 to 7.43, 1 study, 88 women (Analysis 19.3).

This study did not report any of our other secondary outcomes: maternal: fever; urinary tract infection, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Comparison 19 (subgroup 2): Cephalosporin C1 (1st generation) plus nitroimadazole versus broad spectrum penicillin P2

One trial reporting on 139 women (Shah 1998) compared multiple doses of cephradine C1 plus metronidazole N versus a single dose of piperacillin P2. All women had elective caesarean sections. This study was at unclear risk of bias for all domains.

Primary outcomes

Maternal endometritis: RR 2.70, 95% CI 0.63 to 11.55, 1 study, 139 women (Analysis 19.1).

This study did not report our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 2.36, 95% CI 0.84 to 6.62, 1 study, 139 women (Analysis 19.2).

Maternalwound infection: RR 2.02, 95% CI 0.42 to 9.63, 1 study, 139 women (Analysis 19.3).

This study did not report any of our other secondary outcomes: maternal:urinary tract infection, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Comparison 19 (subgroup 3): Cephalosporin C2 (2nd generation) plus nitroimidazole versus broad spectrum penicillin plus betalactamase inhibitors P2+

One study including 83 women (van der Linden 1993) compared multiple doses of cefuroxime C2 plus metronidazole N versus a single dose of co‐amoxyclav (amoxicillin plus clavulanic acid) P2+. Women had mixed elective and non‐elective caesarean sections. There was little information in the trial report and, therefore, this study was at unclear risk of bias for most domains, although there appeared to be no attrition.

Primary outcomes

Maternal endometritis: RR 0.33, 95% CI 0.01 to 7.77, 1 study, 83 women (Analysis 19.1).

This study did not report our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 2.93, 95% CI 0.63 to 13.68, 1 study, 83 women (Analysis 19.2).

Maternalwound infection: RR 0.98, 95% CI 0.06 to 15.09, 1 study, 83 women (Analysis 19.3).

Maternal urinary tract infection: no events, not estimable, 1 study, 83 women (Analysis 19.4).

Costs: the authors commented that "[i]f drug costs only are calculated, the use of AMX/CL [P2+] saves dfl. 30.00/patient, a 60% difference. AMX/CL has the advantage of requiring fewer staff resources and materials associated with administration, and lower cost" (dfl = dutch guilder; now replaced by EUR). This comment reflected the fact that the P2+ group received a single dose, whereas the C2 plus N group received multiple doses. No other cost data were reported.

This study did not report any of our other secondary outcomes: maternal:thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparisons of other antibiotic regimens of multiple classes versus different antibiotic regimens of multiple classes (comparison 20)

For ease of reference, all trials making comparisons that fall within this category have been presented under a single comparison, however, the data have not been totaled because the interventions and comparators varied substantially between trials.

Comparison 20 (subgroup 1): Aminoglycoside A plus nitroimidazole N versus natural penicillin P1 plus nitroimidazole N plus macrolide M

One study reporting on 241 women (Kayihura 2003) compared single doses of gentamicin A plus metronidazole N versus multiple doses of crystalline penicillin P1 plus metronidazole N plus erythromycin M. All women had non‐elective caesarean sections. This study was at unclear risk of selection bias, and high risk of bias due to lack of blinding (both performance and detection bias). There was no evidence of attrition, but unclear risk of selective reporting or other bias.

Primary outcomes

Maternal sepsis: RR 0.81, 95% CI 0.29 to 2.26, 1 study, 241 women (Analysis 20.1).

This study did not report any of our other primary outcomes: maternal endometritis; infant sepsis andoral thrush.

Secondary outcomes

Maternalwound infection: RR 3.23, 95% CI 0.34 to 30.64, 1 study, 241 women (Analysis 20.4).

Maternal urinary tract infection: RR 1.08, 95% CI 0.07 to 17.03, 1 study, 241 women (Analysis 20.5).

Maternal length of hospital stay: MD 0.30 shorter, 95% CI 0.78 shorter to 0.18 longer, 1 study, 241 women (Analysis 20.7).

Costs: the trial report states that "a single dose of prophylactic antibiotics [A plus N] cost USD 0.78 whereas the standard postoperative scheme [P1 plus N plus M] followed at Maputo Central Hospital costs USD 8.37, the former regime thus being less than one‐tenth as expensive as the latter. The costs of the cesarean section, intravenous fluids, nursing and hospital stay are almost the same in both groups".

This study did not report any of our other secondary outcomes: maternal: fever, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparison 20 (subgroup 2): Antistaphylococcal cephalosporins C1 and C2 (1stand 2nd generation) plus nitroimadazole N versus non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

Two studies reporting on a total of 256 women included this comparison (Deng 2007; Rohan 2014). One study including 100 women (Deng 2007) compared multiple doses of cefazolin C1 plus metronidazole N versus multiple doses of benzylpenicillin P1 plus ampicillin P2 plus metronidazole N. The second study including 156 women (Rohan 2014) compared single doses of cefuroxime C2 plus metronidazole N versus single doses of ampicillin P2 plus metronidazole N. All women in both studies had elective caesarean sections.

Both studies had limitations in design. Deng 2007 was at low risk of bias for random sequence generation, but high risk of allocation concealment. This study was also at risk of performance bias, and unclear risk of detection bias. There were no concerns about attrition, however, it was at high risk of selective reporting bias, and unclear risk of selective reporting or other bias. There was little information in the trial report for Rohan 2014, and therefore this study was at unclear risk of bias for most domains, although there appeared to be no attrition.

Primary outcomes

Maternal endometritis: no events, not estimable, 1 study, 156 women (Analysis 20.2).

The studies did not report any of our other primary outcomes: maternal sepsis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 0.72, 95% CI 0.13 to 4.14, 1 study, 100 women (Analysis 20.3).

Maternalwound infection: RR 2.00, 95% CI 0.19 to 21.61, 2 studies, 256 women (Analysis 20.4).

Maternal urinary tract infection: no events, not estimable, 1 study, 156 women (Analysis 20.5).

Maternal composite adverse events: no events, not estimable, 1 study, 100 women (Analysis 20.6).

Maternal length of hospital stay: MD 0.53 shorter (unit assumed to be days from quantities reported), 95% CI 1.36 shorter to 0.30 longer, 1 study, 100 women (Analysis 20.7).

Costs: renminbi (RMB) 136.12 lower, 95% CI RMB 165.73 lower to RMB 106.51 lower, 1 study, 100 women (Analysis 20.8).

This study did not report any of our other secondary outcomes:maternal: thrush, serious infectious complication, specific adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development.

Comparison 20 (subgroup 3): Cephalosporin C3 (3rd generation) plus nitroimidazole N versus natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

One study reporting on 232 women (Gidiri 2014) compared single doses of ceftriaxone C3 plus metronidazole N versus multiple doses of benzyl penicillin P1 plus amoxicillin P2 plus metronidazole N plus chloramphenicol Am. Women had mixed elective and non‐elective caesarean sections. This study was at unclear risk of bias for random sequence generation, and high risk due to concerns about concealment of allocation. There was high risk of performance bias, but risk of detection bias was unclear. There was no evidence of attrition, but unclear risk of selective reporting or other bias.

Primary outcomes

Maternal sepsis: RR 3.21, 95% CI 0.34 to 30.45, 1 study, 232 women (Analysis 20.1).

This study did not report any of our other primary outcomes: maternal endometritis; infant sepsis andoral thrush.

Secondary outcomes

Maternal fever (febrile morbidity): RR 1.22, 95% CI 0.46 to 3.27, 1 study, 232 women (Analysis 20.3).

Maternalwound infection: RR 1.29, 95% CI 0.40 to 4.10, 1 study, 232 women (Analysis 20.4).

Costs: this study provides some incomplete information relating to the costs of the drugs in each group, stating that the cost to the woman of the specified single doses of ceftriaxone plus metronidazole is USD 3, versus USD 10 for antibiotics in the P2 group (USD 10 appears to be the cost per dose; and the women would receive at least 13 doses according to the standard regimen given to the control group in this study).

This study did not report any of our other secondary outcomes: maternal: fever, urinary tract infection, thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant: immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Other comparisons (lavage administration)

Two trials administered different classes of antibiotics by lavage. Both trials compared cephalosporins versus penicillins.

Data from Dashow 1986, which randomised 204 women to receive cephapirin C1 versus cefamandole C2 versus ampicillin P2, were not included in this update due to inconsistencies in the denominators in the trial report.

The other trial (Lewis 1990) reported data on 383 women. This trial compared lavage with cefoxitin C2 versus lavage with ticarcillin P2. Women had mixed elective and non‐elective caesarean sections. This study was at unclear risk of bias for all domains except performance bias (low risk) and selective reporting (high risk) due to lack of reporting of some outcomes for elective caesarean sections (unlike non‐elective caesarean sections).

Comparison 21 (subgroup 1): Cephalosporins C2 (2nd generation) versus broad spectrum penicillin P2
Primary outcomes

Maternal endometritis: RR 0.95, 95% CI 0.63 to 1.43, 1 study, 383 women (Analysis 21.1).

This study also reported on maternal septicaemia. While these results are relevant to consideration of maternal sepsis, we have not included data in our analyses because the report only included information relating to women who had non‐elective caesarean sections (0/135 versus 0/152), and did not report results for women who had elective caesarean sections, or explain why they had not done so.

Secondary outcomes

Maternal fever (febrile morbidity): RR 0.95, 95% CI 0.63 to 1.43, 1 study, 383 women (Analysis 21.2).

Maternal wound infection: RR 1.06, 95% CI 0.27 to 4.17, 1 study, 383 women (Analysis 21.3).

This study also reported on urinary tract infection, however again data were only reported for women who had non‐elective caesarean sections (5/135 versus 3/152), and not for women who had elective caesarean section, therefore we have not included these data in our analyses.

This study did not report any of our other secondary outcomes: maternal:thrush, serious infectious complication, adverse effects (allergic reactions, nausea, vomiting, diarrhoea, skin rash), length of hospital stay,infections,readmissions; infant:immediate adverse effects (unsettled, diarrhoea, rashes), length of hospital stay, long‐term adverse effects (general health, frequency of hospital visits),immune system development; costs.

Publication bias

There were insufficient numbers of studies in all our comparisons to assess publication bias.

Sensitivity analyses

There were insufficient data from high‐quality studies for any meaningful sensitivity analyses.

Discussion

Antibiotic prophylaxis can be expected to produce a significant reduction in the incidence of maternal infectious morbidity (Smaill 2014). The type of antibiotic used prophylactically, as well as the optimal timing of administration, have been widely studied and discussed in the literature. Here we have addressed the comparisons between the different classes of antibiotics.

Summary of main results

Eight trials involving 1540 women contributed data to our main comparison of antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors (systemic administration). There may be little or no difference between these antibiotics in their ability to prevent endometritis and there was too little data to report on maternal sepsis. There was no conclusive evidence identified of any important difference between them for maternal fever, wound infection, urinary tract infection and maternal adverse effects.

For the other comparisons of specific types of cephalosporins versus specific types of penicillins, the findings were similarly inconclusive, although minimally antistaphylococcal cephalosporins (3rd generation) may be more effective than non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) in preventing maternal endometritis.

We did not identify any clear difference between other single classes of antibiotics, or for comparisons including multiple classes in one or both groups, for any clinical outcomes. However, we only identified small single studies for all but one of these comparisons, and more data are needed.

None of the studies assessed any infant outcomes. Most of the studies administered antibiotics at or after cord clamping. Best practice has now changed based on new evidence to support administration of antibiotics before skin incision (Mackeen 2014). This is a potential source of bias that could interfere with the results reported in this review. There is a need for further investigation of the efficacy and safety of different classes of antibiotics given prior to skin incision.

The absence of evidence on infant outcomes is a serious omission, as women will want to know if this intervention has any adverse effect on their babies. The absence of this information remains a concern even for studies where the antibiotic was given after the cord had been clamped and cut, as these drugs may pass to the baby through breastfeeding. In addition, none of the studies assessed readmissions and only three considered post‐discharge infections. This is a limitation of this analysis as late infections appear to constitute the majority of infections after caesarean section (Leth 2009). We have no information on whether prophylactic antibiotics impact on these infections and whether one class of antibiotic is better than another.

We also found very little difference on maternal side effects which can have different degrees of severity but can also be cumbersome for some women postpartum. The lack of information also warrants further investigation. We have found most of the outcomes to refer to in‐hospital infections, whereas surveillance should cover up to 30 days after the operation due to the fact that surgical site infections are frequently diagnosed post‐discharge (Sarah 2019).

Overall, 19 studies provided information or commented on costs of antibiotic prophylaxis, however in most cases this information was minimal. Given the limited and patchy cost data reported, it was not possible to provide a comprehensive picture of the relative costs or cost‐effectiveness of the wide array of antibiotics considered in the included studies. The relevance of cost information was also limited by substantial variation in the study dates and geographical locations.

Overall completeness and applicability of evidence

No trials addressed two of our three main comparisons. Due to the very large number of different comparisons made in different trials, of either different single classes or sub‐types of drugs, or diverse combinations of drugs, there were insufficient data to draw any firm conclusions about specific comparisons.

Other Cochrane Reviews have been undertaken that address specifically the timing (Mackeen 2014) and routes of administration (Nabhan 2016) of prophylactic antibiotics for preventing infectious morbidity in women undergoing caesarean section. In this review, most trials administered antibiotics at or after cord clamping, or post‐operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision (Mackeen 2014). We anticipate that the comparisons between the specific subclasses of penicillins and cephalosporins will also be more fully addressed in further (as yet unpublished) Cochrane Reviews (Different regimens of penicillin antibiotic given to women routinely for preventing infection after caesarean section and Different regimens of cephalosporin antibiotic given to women routinely for preventing infection after caesarean section); however, if these reviews remain unpublished, inclusion of intra‐class comparisons in a future update of the current review may be warranted. 

Most trials in this review were undertaken some years ago, and patterns of antibiotic resistance may have changed in the intervening period; due to changing resistance patterns in different locations, choice of drug may need to be tailored to local circumstances.

Quality of the evidence

The risk of bias for most domains as assessed in the included studies was often unclear, possibly due to the inclusion of many older trials where the study design was not adequately reported, so as to rule out important possible risk of bias. For our main comparison of antistaphylococcal cephalosporins (1st and 2nd generation) and broad spectrum penicillins plus betalactamase inhibitors, the certainty of the evidence using GRADE was low for maternal endometritis, and very low for maternal sepsis, wound infection, urinary tract infection, and maternal composite adverse effects (summary of findings Table 1). The outcomes were largely downgraded due to concerns about design limitations, wide confidence intervals crossing the line of no effect, and few events.

Potential biases in the review process

We attempted to minimise bias in a number of ways: two review authors assessed eligibility for inclusion and carried out data extraction, and at least two authors assessed risk of bias. Each worked independently. Nevertheless, the process of assessing risk of bias, for example, is not an exact science and includes many personal judgements.

Agreements and disagreements with other studies or reviews

The previous version of this review concluded that there was no difference in efficacy between cephalosporins and penicillins when used to prevent infection in women undergoing caesarean section (Gyte 2014), however for this update we did not pool all cephalosporins or all penicillins. Nevertheless, the evidence available for this update was similar in that it did not support strong conclusions that one type of drug was beneficial when compared to another, nor that there was no difference between them, when all important outcomes signalling both safety and efficacy are considered. While we did not aim to investigate variations in regimen in this review, an earlier version of the review found no benefit from multiple doses as opposed to a single dose of antibiotics. This issue will hopefully be addressed in the remaining two reviews to be undertaken (Different regimens of penicillin antibiotic given to women routinely for preventing infection after caesarean section and Different regimens of cephalosporin antibiotic given to women routinely for preventing infection after caesarean section). The Cochrane Review on the timing of administration of prophylactic antibiotics at caesarean section suggests that preoperative administration is more effective (Mackeen 2014), however that review did not report on longer‐term adverse effects for the baby (while our review did not find evidence on long‐term outcomes for the baby). A further Cochrane Review on route of administration of antibiotic prophylaxis for women undergoing caesarean section did not yield any conclusions regarding the relative efficacy of different routes, due to a lack of good‐quality evidence (Nabhan 2016). In light of this uncertainty, for this update we did not pool data from systemic administration with lavage, due to known differences in the way that drugs are absorbed when given via irrigation rather than systemically.

While slightly different in scope, another systematic review relating to this topic also emphasised that the absence of evidence on neonatal outcomes ‐ especially in the context of administration pre‐incision ‐ needs to the addressed, and that microbial resistance should also be studied and factored into decision‐making (Tita 2009).

Study flow diagram.

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Figure 1

Study flow diagram.

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 1: Maternal sepsis

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Analysis 1.1

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 1: Maternal sepsis

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 2: Maternal endometritis

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Analysis 1.2

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 2: Maternal endometritis

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

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Analysis 1.3

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 4: Maternal wound infection

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Analysis 1.4

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 4: Maternal wound infection

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 5: Maternal urinary tract infection

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Analysis 1.5

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 5: Maternal urinary tract infection

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 6: Maternal composite adverse effects

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Analysis 1.6

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 6: Maternal composite adverse effects

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 7: Maternal allergic reactions

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Analysis 1.7

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 7: Maternal allergic reactions

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Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 8: Maternal skin rash

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Analysis 1.8

Comparison 1: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 8: Maternal skin rash

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Comparison 2: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 1: Maternal sepsis

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Analysis 2.1

Comparison 2: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 1: Maternal sepsis

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Comparison 2: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 2: Maternal endometritis

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Analysis 2.2

Comparison 2: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 2: Maternal endometritis

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Comparison 3: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin, Outcome 1: Maternal sepsis

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Analysis 3.1

Comparison 3: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin, Outcome 1: Maternal sepsis

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Comparison 3: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin, Outcome 2: Maternal endometritis

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Analysis 3.2

Comparison 3: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin, Outcome 2: Maternal endometritis

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 1: Maternal endometritis

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Analysis 4.1

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 1: Maternal endometritis

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 2: Sensitivity analysis (Fixed effects) Maternal endometritis

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Analysis 4.2

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 2: Sensitivity analysis (Fixed effects) Maternal endometritis

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

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Analysis 4.3

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 4: Subgroup analysis by type of cephalosporin Maternal fever (febrile morbidity)

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Analysis 4.4

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 4: Subgroup analysis by type of cephalosporin Maternal fever (febrile morbidity)

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 5: Maternal wound infection

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Analysis 4.5

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 5: Maternal wound infection

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 6: Maternal urinary tract infection

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Analysis 4.6

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 6: Maternal urinary tract infection

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 7: Maternal composite adverse effects

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Analysis 4.7

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 7: Maternal composite adverse effects

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 8: Maternal allergic reactions

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Analysis 4.8

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 8: Maternal allergic reactions

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Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 9: Maternal length of hospital stay (days)

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Analysis 4.9

Comparison 4: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 9: Maternal length of hospital stay (days)

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Comparison 5: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 1: Maternal endometritis

Figures and Tables -
Analysis 5.1

Comparison 5: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 1: Maternal endometritis

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Comparison 6: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by generation of cephalosporin, Outcome 1: Maternal endometritis

Figures and Tables -
Analysis 6.1

Comparison 6: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by generation of cephalosporin, Outcome 1: Maternal endometritis

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Comparison 7: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 1: Maternal endometritis

Figures and Tables -
Analysis 7.1

Comparison 7: Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 1: Maternal endometritis

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 1: Maternal sepsis

Figures and Tables -
Analysis 8.1

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 1: Maternal sepsis

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 2: Maternal endometritis

Figures and Tables -
Analysis 8.2

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 2: Maternal endometritis

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

Figures and Tables -
Analysis 8.3

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 3: Maternal fever (febrile morbidity)

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 4: Maternal wound infection

Figures and Tables -
Analysis 8.4

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 4: Maternal wound infection

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 5: Maternal urinary tract infection

Figures and Tables -
Analysis 8.5

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 5: Maternal urinary tract infection

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 6: Maternal composite serious infectious complication

Figures and Tables -
Analysis 8.6

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 6: Maternal composite serious infectious complication

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 7: Maternal composite adverse effects

Figures and Tables -
Analysis 8.7

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 7: Maternal composite adverse effects

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 8: Maternal allergic reactions

Figures and Tables -
Analysis 8.8

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 8: Maternal allergic reactions

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 9: Maternal nausea

Figures and Tables -
Analysis 8.9

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 9: Maternal nausea

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 10: Maternal vomiting

Figures and Tables -
Analysis 8.10

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 10: Maternal vomiting

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 11: Maternal diarrhoea

Figures and Tables -
Analysis 8.11

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 11: Maternal diarrhoea

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Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 12: Maternal skin rash

Figures and Tables -
Analysis 8.12

Comparison 8: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes, Outcome 12: Maternal skin rash

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Comparison 9: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 1: Maternal sepsis

Figures and Tables -
Analysis 9.1

Comparison 9: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 1: Maternal sepsis

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Comparison 9: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 2: Maternal endometritis

Figures and Tables -
Analysis 9.2

Comparison 9: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS, Outcome 2: Maternal endometritis

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Comparison 10: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 1: Maternal sepsis

Figures and Tables -
Analysis 10.1

Comparison 10: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 1: Maternal sepsis

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Comparison 10: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 2: Maternal endometritis

Figures and Tables -
Analysis 10.2

Comparison 10: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin, Outcome 2: Maternal endometritis

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 1: Maternal endometritis

Figures and Tables -
Analysis 11.1

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 1: Maternal endometritis

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 2: Maternal fever (febrile morbidity)

Figures and Tables -
Analysis 11.2

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 2: Maternal fever (febrile morbidity)

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 3: Maternal wound infection

Figures and Tables -
Analysis 11.3

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 3: Maternal wound infection

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 4: Maternal urinary tract infection

Figures and Tables -
Analysis 11.4

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 4: Maternal urinary tract infection

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 5: Maternal composite serious infectious complication

Figures and Tables -
Analysis 11.5

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 5: Maternal composite serious infectious complication

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 6: Maternal composite adverse effects

Figures and Tables -
Analysis 11.6

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 6: Maternal composite adverse effects

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 7: Maternal allergic reactions

Figures and Tables -
Analysis 11.7

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 7: Maternal allergic reactions

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 8: Maternal nausea

Figures and Tables -
Analysis 11.8

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 8: Maternal nausea

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 9: Maternal vomiting

Figures and Tables -
Analysis 11.9

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 9: Maternal vomiting

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 10: Maternal diarrhoea

Figures and Tables -
Analysis 11.10

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 10: Maternal diarrhoea

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 11: Maternal skin rash

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Analysis 11.11

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 11: Maternal skin rash

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Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 12: Maternal length of hospital stay

Figures and Tables -
Analysis 11.12

Comparison 11: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes, Outcome 12: Maternal length of hospital stay

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Comparison 12: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 1: Maternal endometritis

Figures and Tables -
Analysis 12.1

Comparison 12: Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS, Outcome 1: Maternal endometritis

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Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 1: Maternal endometritis

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Analysis 13.1

Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 1: Maternal endometritis

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Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Analysis 13.2

Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 3: Maternal wound infection

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Analysis 13.3

Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 3: Maternal wound infection

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Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 4: Maternal vomiting

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Analysis 13.4

Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 4: Maternal vomiting

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Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 5: Maternal skin rash

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Analysis 13.5

Comparison 13: Other cephalosporin (only) regimens vs other penicillin (only) regimens, Outcome 5: Maternal skin rash

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Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 1: Maternal sepsis

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Analysis 14.1

Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 1: Maternal sepsis

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Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 2: Maternal endometritis

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Analysis 14.2

Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 2: Maternal endometritis

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Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 3: Maternal wound infection

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Analysis 14.3

Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 3: Maternal wound infection

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Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 4: Maternal urinary tract infection

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Analysis 14.4

Comparison 14: Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+, Outcome 4: Maternal urinary tract infection

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Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 1: Maternal sepsis

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Analysis 15.1

Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 1: Maternal sepsis

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Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 2: Maternal endometritis

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Analysis 15.2

Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 2: Maternal endometritis

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Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 3: Maternal wound infection

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Analysis 15.3

Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 3: Maternal wound infection

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Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 4: Maternal urinary tract infection

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Analysis 15.4

Comparison 15: Fluoroquinolones F vs cephalosporins C2 (2nd generation), Outcome 4: Maternal urinary tract infection

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Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 1: Maternal endometritis

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Analysis 16.1

Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 1: Maternal endometritis

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Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 2: Maternal fever (febrile morbidity)

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Analysis 16.2

Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 2: Maternal fever (febrile morbidity)

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Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 3: Maternal wound infection

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Analysis 16.3

Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 3: Maternal wound infection

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Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 4: Maternal urinary tract infection

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Analysis 16.4

Comparison 16: Carbapenems Ca vs cephalosporins C3 (3rd generation), Outcome 4: Maternal urinary tract infection

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Comparison 17: Macrolides M vs cephalosporins C1 (1st generation), Outcome 1: Maternal fever (febrile morbidity)

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Analysis 17.1

Comparison 17: Macrolides M vs cephalosporins C1 (1st generation), Outcome 1: Maternal fever (febrile morbidity)

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 1: Maternal endometritis

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Analysis 18.1

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 1: Maternal endometritis

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Analysis 18.2

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 3: Maternal wound infection

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Analysis 18.3

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 3: Maternal wound infection

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 4: Maternal urinary tract infection

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Analysis 18.4

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 4: Maternal urinary tract infection

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 5: Maternal length of hospital stay (days)

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Analysis 18.5

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 5: Maternal length of hospital stay (days)

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Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 6: Costs

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Analysis 18.6

Comparison 18: Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens, Outcome 6: Costs

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Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 1: Maternal endometritis

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Analysis 19.1

Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 1: Maternal endometritis

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Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Analysis 19.2

Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 2: Maternal fever (febrile morbidity)

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Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 3: Maternal wound infection

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Analysis 19.3

Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 3: Maternal wound infection

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Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 4: Maternal urinary tract infection

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Analysis 19.4

Comparison 19: Other antibiotic regimens (multiple classes) vs penicillin (only) regimens, Outcome 4: Maternal urinary tract infection

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 1: Maternal sepsis

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Analysis 20.1

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 1: Maternal sepsis

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 2: Maternal endometritis

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Analysis 20.2

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 2: Maternal endometritis

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 3: Maternal fever (febrile morbidity)

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Analysis 20.3

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 3: Maternal fever (febrile morbidity)

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 4: Maternal wound infection

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Analysis 20.4

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 4: Maternal wound infection

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 5: Maternal urinary tract infection

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Analysis 20.5

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 5: Maternal urinary tract infection

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 6: Maternal composite adverse effects

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Analysis 20.6

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 6: Maternal composite adverse effects

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 7: Maternal length of hospital stay

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Analysis 20.7

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 7: Maternal length of hospital stay

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Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 8: Costs

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Analysis 20.8

Comparison 20: Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes), Outcome 8: Costs

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Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 1: Maternal endometritis

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Analysis 21.1

Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 1: Maternal endometritis

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Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 2: Maternal fever (febrile morbidity)

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Analysis 21.2

Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 2: Maternal fever (febrile morbidity)

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Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 3: Maternal wound infection

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Analysis 21.3

Comparison 21: (Irrigation/lavage) cephalosporins vs penicillins, Outcome 3: Maternal wound infection

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Summary of findings 1. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section

Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section

Patient or population: all women undergoing caesarean section
Setting: Hospital (Greece, India, Thailand, USA)
Intervention: antistaphylococcal cephalosporins 1st and 2nd generation (C1 and C2)
Comparison: broad spectrum penicillins plus betalactamase inhibitors (P2+)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with broad spectrum penicillins plus betalactamase inhibitors (P2+)

Risk with Antistaphylococcal cephalosporins (1st and 2nd generation (C1 and C2)

Maternal sepsis

Study population

RR 2.37
(0.10 to 56.41)

75
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

0 per 1000

0 per 1000
(0 to 0)

Maternal endometritis

Study population

RR 1.10
(0.76 to 1.60)

1161
(7 RCTs)

⊕⊕⊝⊝
LOW 1 3

78 per 1000

86 per 1000
(60 to 125)

Infant sepsis

Study population

‐

(0 studies)

‐

No included studies reported on this outcome

see comment

see comment

Infant oral thrush

Study population

‐

(0 studies)

‐

No included studies reported on this outcome

see comment

see comment

Maternal wound infection

Study population

RR 0.78
(0.32 to 1.90)

543
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 4 5

38 per 1000

29 per 1000
(12 to 71)

Maternal urinary tract infection

Study population

RR 0.64
(0.11 to 3.73)

496
(4 RCTs)

⊕⊝⊝⊝
VERY LOW
6 7 8

51 per 1000

33 per 1000
(6 to 190)

Maternal composite adverse effects

Study population

RR 0.96
(0.09 to 10.50)

468
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 4 5

5 per 1000

5 per 1000
(0 to 56)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

1 All of pooled effect provided by study or studies at moderate risk of selection bias. Downgrade ‐1.

2 Single study with small sample size and few events. Wide confidence interval including both appreciable reduction and appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins. The reported data are for bacteriaemia, not sepsis. Although bacteriaemia is usually accompanied by sepsis, there is the possibility of indirectness for this outcome. Downgrade ‐2.

3 Wide confidence interval including appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins, whilst also including no difference in effect. Downgrade ‐1.

4 Majority of pooled effect provided by studies at moderate risk of selection bias or detection bias. Downgrade ‐1.

5 Few events. Wide confidence interval including both appreciable reduction and appreciable increase in risk with antistaphylococcal (1st and 2nd generation) cephalosporins. Downgrade ‐2.

6 Majority of pooled effect provided by studies at moderate risk of bias due to lack of information about random sequence generation and concealment of allocation. Downgrade ‐1.

7 Severe unexplained statistical heterogeneity (I2 = 66%, P value for Chi2 test = 0.05). Downgrade ‐1.

8 Few events. Downgrade ‐1.

Figures and Tables -
Summary of findings 1. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) compared to broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes for preventing infection at caesarean section
Navigate to table in Review
Table 1. Classification of antibiotics

Penicillins (P)

Penicillins consist of a thiazolidine ring connected to a B‐lactam ring to which is attached to a side chain. The penicillin nucleus itself is the chief structural requirement for biological activity. Penicillins are the oldest class of antibiotics and function by inhibiting cell wall synthesis (bactericidal).

Class or sub‐class name and detail

Examples

Spectrum

Natural penicillins (P1) are based on the original penicillin‐G structure (also known as first‐generation penicillins)

Penicillin G (benzyl penicillin, crystalline penicillin); Procaine; Penicillin V; Benzathine.

Gram‐positive: non‐betalactamase producing gram‐positive cocci (including viridans streptococci, group A streptococci, Streptococcus pneumoniae, anaerobic Streptococcus), Enterococcus spp., non‐penicillinase producing strains of Staphylococcus aureus, coagulase negative Staphylococcus aureus, Clostridium spp. (excluding C. difficile), Actinomyces spp

Gram‐negative:Neisseria meningitides, non‐penicillinase producing Neisseria gonorrhoea, Pasteurella multocida

Broad spectrum penicillins(P2) which are effective against a wider range of bacteria

Second‐generation penicillins:

Aminopenicillins; Ampicillin; Amoxicillin.

Gram‐positive:Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes.

Gram negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae Anaerobes: Clostridium spp

Third‐generation penicillins:
Carbenicillin; Ticarcillin.

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes.

Gram‐negative: Escherichia coli, Proteus mirabilis, Salmonella, Shigella, Haemophilus influenzae, Pseudomonas aeruginosa, Acinetobacter spp

Anaerobes: Clostridium spp

Fourth‐generation penicillins:
Piperacillin; Mezlocillin.

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus.

Gram‐negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae

Anaerobes: Clostridium spp, Bacteroides fragilis

Penicillins plus betalactamase inhibitors (P2+) are active against gram‐positive, gram‐negative and anaerobic bacteria, including S.aureus, Enterococci, Streptococci, many Enterobacterales and Bacteroides spp

Co‐amoxyclav = amoxicillin + clavulanic acid (Trade names include: Augmentin; Clavamox; Tyclav)
Ampicillin + sulbactam (Trade names include: Ampictam; Unasyn)
Timentin = ticarcillin + clavulanate

Gram‐positive: Streptococcus spp, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus.

Gram‐negative:Escherichia coli, Proteus mirabilis, Salmonella, Shigella, e Haemophilus influenzae

Anaerobes: Clostridium spp, Bacteroides fragilis

Antistaphylococcal penicillins(P3) are active even in the presence of the bacterial enzyme that inactivates most natural penicillins (also known as penicillinase‐resistant penicillins)

Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin.

Staphylococcus aureus

Cephalosporins (C)

Cephalosporins have a similar basic structure to penicillins but with different side chains. They function by inhibiting cell wall synthesis.

First‐generation cephalosporins (C1)

Cephalothin; cefazolin; cephapirin; cephradine; cephalexin; cefadroxil.

Gram‐positive: (Streptococcus spp, Staphylococcus aureus) Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae

Anaerobes: except Bacteroides

Second‐generation cephalosporins (C2)

Cefoxitin; cefaclor; cefuroxime; cefotetan; cefprozil; cefamandole, cefonicid; ceforanide, cefotiam.

Gram‐positive: (Streptococcus spp, Staphylococcus aureus) Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae.

Anaerobes: including Bacteroides (Cephamycins)

Third‐generation cephalosporins (C3)

Cefotaxime; ceftizoxime; ceftriaxone; cefpodoxime; cefditoren; ceftibuten; ceftazidime; cefcapene; cefdaloxime; cefetamet; cefixime; cefmenoxime; cefodizime; cefoperazone; cefpimizole.

Gram‐negative: Enterobacterales, Neisseria spp, Haemophilus spp

Gram‐positive: Streptococcus spp

Anaerobes:Bacteroides fragilis, Clostridium spp, Peptostreptococcus spp, Prevotella sp

Fourth‐generation cephalosporins (C4)

Cefepime; cefpirome; cefclidine; cefluprenam; cefozopran; cefquinome.

Gram‐negatives: Enterobacterales, Neisseria spp, Haemophilus spp, Acinetobacter spp, Pseudomonas aeruginosa
Gram‐positive:Staphylococcus aureus, Streptococcus spp

Cephalosporin plus betalactamase inhibitors (C+)

Ceftolozane‐tazobactam; ceftazidime‐avibactam.

Ceftolozane‐tazobactam

Gram‐negative:Enterobacterales, P aeruginosa, Gram‐positive: limited activity against streptococci, general low activity against staphilococcal and enterococcal species.

Ceftzidime‐avibactam extends the spectrum of ceftazidime against AmpC beta‐lactamase, ESBL and some specific carbapenemases

Other classes of antibiotics

Aminoglycosides (A) are first‐line therapy for a limited number of very specific, often historically prominent infections, such as plague, tularemia and tuberculosis. They are used to treat resistant infections caused by Gram‐negative bacilli

Streptomycin; gentamicin, kanamycin, amikacin.

Gram‐negative: Enterobacterales, Pseudomonas spp, Acinetobacter spp

Synergism with beta‐lactams and glycopeptides Enterococcus spp and S. aureus

Amphenicols (Am) inhibit bacterial protein synthesis. Very rarely used nowadays.

Chloramphenicol

Chloramphenicol is considered to have similar action to tetracycline (see below).

Other beta‐lactams: carbapenems (Ca) Carbapenems are beta‐lactams that have a broader spectrum of activity than most other beta‐lactam antibiotics.

Examples include Imipenem; meropenem; ertapenem; aztreonam.

Gram‐negative: including Extended‐sectrum betalactamase producing bacteria (ESBL+), H. influenzae e N. gonorrhoeae, Enterobacterales, Acinetobacter spp, P. aeruginosa
Gram‐positive: including Enterococcus faecalis, Listeria S. aureus

Anaerobes: including B. fragilis

Fluoroquinolones (F) target the bacterial DNA gyrase and topoisomerase. They are potent bacteriocidal agents against a broad variety of micro‐organisms.

Ciprofloxacin; levofloxacin; lomefloxacin; norfloxacin; sparfloxacin; clinafloxacin; gatifloxacin; ofloxacin; trovafloxacin, maxifloxacin.

Gram‐negative: Enterobacterales, Pseudomonas spp, Acinetobacter spp

Moxifloxacin and Levofloxacin: as above plus Streptococci

Lincosamides (L) are protein synthesis inhibitors which bind to the 50s subunit of bacterial ribosomes and inhibit early elongation of peptide chain by inhibiting transpeptidase reaction.

Lincomycin; clindamycin.

Gram‐positive aerobes and anaerobes, including S. Aureus and Streptococci, not Enterococci

Macrolides (M) inhibit bacterial protein synthesis. Resistance can arise.

Erythromycin; clarithromycin; azithromycin.

Streptococcus pneumoniae,S. aureus, Listeria monocytogenes, Neisseria spp, Chlamydia spp, Legionella spp, Haemophilus spp

Nitroimidazoles (N) Nitroimidazole is an imidazole derivative that contains a nitro group. It is used for the treatment of infection with anaerobic organisms.

Metronidazole; tinidazol.

Clostridium spp, Eubacterium spp, Peptococcus spp, Peptostreptococcus spp, Fusobacterium spp, Gardnerella, Mobiluncus, Trichomonas, Entamoeba spp

Tetracyclines (T) are bacteriostatic antibiotics active against a wide range of aerobes and anaerobic gram‐positive and gram‐negative bacteria. They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome.

Tetracyclines should not be used with children under 8 and specifically during teeth development as they can cause a permanent brown discolouration to the teeth. This antibiotic is, therefore, unlikely to be used at caesarean section.

Tetracycline; doxycycline; minocycline.

Staphylococcus aureus, Streptococcus pneumonia, Streptococcus pyogenes, Streptooccus agalacticae, Campylobacter jejuni, Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitides,Clostridium spp., Peptostreptococcus spp., Peptococcus spp. Bacteroides melaninogenicus, Bacteroides fragilis

This table was originally adapted from information at https://www.emedexpert.com/classes/antibiotics.shtml, and has been revised for the 2020 update (Drew 2020; Letourneau 2020a; Letourneau 2020b; Letourneau 2020c; Letourneau 2020d; WHO 2020.

Figures and Tables -
Table 1. Classification of antibiotics
Navigate to table in Review
Table 2. Comparison matrix

Intervention/comparison class
or sub‐class of
antibiotic

Single class administered

Multiple classes administered

Antistaphylococcal cephalosporins (C1 and C2; 1st and 2nd generation)

Minimally antistaphylococcal cephalosporins (C3; 3rd generation)

Broad spectrum penicillins plus betalactamase inhibitors (P2+)

Lincosamide (L) plus aminoglycoside (A)

Antistaphylococcal cephalosporins (C1 and C2; 1st and 2nd generation) plus nitroimadazole (N)

Aminoglycaside (A) plus nitroimidazole (N)

Minimally antistaphylococcal cephalosporins (C3; 3rd generation) plus nitroimidazole (N)

Single class administered

Broad spectrum penicillins plus betalactamase inhibitors (P2+)

8 trials
(1540 women)

2 trials
(865 women)

Comparison not within scope of review

No trials

1 trial

(83 women)

No trials

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum)

Systemic administration:
9 trials
(3093 women)

Lavage: 1 trial (383 women)

4 trials
(854 women)

Comparison not within scope of review

1 trial

(88 women)

1 trial

(139 women)

No trials

No trials

Broad spectrum penicillins (P2) and antistaphylococcal penicillins (P3)

No trials

1 trial
(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Fluoroquinolones (F)

1 trial

(81 women)

No trials

1 trial

(72 women)

No trials

No trials

No trials

No trials

Carbapenems (Ca)

No trials

1 trial

(48 women)

No trials

No trials

No trials

No trials

No trials

Macrolides (M)

1 trial

(70 women)

No trials

No trials

No trials

No trials

No trials

No trials

Multiple classes administered

Broad spectrum penicillin (P2) plus antistaphylococcal penicillin (P3) plus aminoglycoside (A) plus nitroimadazole (N)

No trials

1 trial

(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Antistaphylococcal penicillin (P3) plus aminoglycoside (A)

No trials

1 trial

(200 women)

Comparison not within scope of review

No trials

No trials

No trials

No trials

Natural penicillin (P1) plus nitroimidazole (N) plus macrolide (M)

No trials

No trials

Comparison not within scope of review

No trials

No trials

1 trial
(241 women)

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum) plus nitroimadazole (N)

No trials

No trials

Comparison not within scope of review

No trials

2 trials
(256 women)

No trials

No trials

Non‐antistaphylococcal penicillins (P1 and P2; natural and broad spectrum) plus nitroimadazole (N) plus amphenicol (Am)

No trials

No trials

Comparison not within scope of review

No trials

No trials

No trials

1 trial

(232 women)
Figures and Tables -
Table 2. Comparison matrix
Navigate to table in Review
Table 3. Interventions: drugs and doses

Antistaphylococcal cephalosporins (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors

(8 trials, 1 540 women)

Antistaphylococcal cephalosporins (1st and 2nd generation)

vs

Broad spectrum penicillins plus betalactamase inhibitors

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefazolin

1 g single dose

289

Ampicillin plus sulbactam

1 g single dose

87

2 g single dose

67

1.5 g single dose

128

Cefotetan

1 g single dose

224

3 g single dose

192

2 g single dose

96

Co‐amoxyclav (amoxicillin plus clavulanic acid)

1.2 g single dose

188

Cefoxitin

2 g x 3 doses

68

2.4 g single dose

55

Cefuroxime

1.5 g single dose

85

Ticarcillin plus clavulanic acid

(3 g + 100 mg)
x 3 doses

61

Antistaphylococcal cephalosporins (1st and 2nd generation) vs non‐antistaphylococcal penicillins (natural and broad spectrum)

(9 trials, 3 093 women)

Antistaphylococcal cephalosporins (1st and 2nd generation)

vs

Non‐antistaphylococcal penicillins (natural and broad spectrum)

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefazolin

1 g single dose

283

Ampicillin

2 g single dose

315

2 g single dose

161

1 g x 3 doses

113

1 g x 3 doses

261

Benzathine penicillin; and

Procaine penicillin

(1 200 000 IU and

400 000 IU) x 5 doses

200

Cefonicid

1 g

147

Mezlocillin

4 g single dose

51

Cefotetan

2 g, single dose

244

2 g x 3 doses

51

Cefoxitin

1 g single dose

155

Piperacillin

4 g single dose

155

2 g single dose

162

2 g x 3 doses

268

2 g x 3 doses

278

4 g x 3 doses

49

Cephalothin

2 g single dose

200

Minimally antistaphylococcal cephalosporins (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors

(2 trials, 865 women)

Minimally antistaphylococcal cephalosporins (3rd generation)

vs

Broad spectrum penicillins plus betalactamase inhibitors

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefotaxime

1 g single dose

431

Co‐amoxyclav (amoxicillin plus clavulanic acid)

1.2 g single dose

434

Minimally antistaphylococcal cephalosporins (3rd generation) vs non‐antistaphylococcal penicillins (natural and broad spectrum)

(4 trials, 854 women)

Minimally antistaphylococcal cephalosporins (3rd generation)

vs

Non‐antistaphylococcal penicillins (natural and broad spectrum)

Drug

Dose

Number of women

Drug

Dose

Number of women

Cefotaxime

1 g x 3

55

Ampicillin

2 g

148

Ceftizoxime

1 g

135

1 g x 3

59

Ceftriaxone

1 g

145

1 g x 1;
then 500mg x 4

125

Mezlocillin

2 g

32

Piperacillin

4 g

155
Figures and Tables -
Table 3. Interventions: drugs and doses
Navigate to table in Review
Comparison 1. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Maternal sepsis Show forest plot

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.37 [0.10, 56.41]

1.2 Maternal endometritis Show forest plot

7

1161

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.76, 1.60]

1.3 Maternal fever (febrile morbidity) Show forest plot

3

678

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.65, 1.75]

1.4 Maternal wound infection Show forest plot

4

543

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.32, 1.90]

1.5 Maternal urinary tract infection Show forest plot

4

496

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.11, 3.73]

1.6 Maternal composite adverse effects Show forest plot

2

468

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.09, 10.50]

1.7 Maternal allergic reactions Show forest plot

2

373

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

1.8 Maternal skin rash Show forest plot

3

591

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.28, 4.11]
Figures and Tables -
Comparison 1. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes
Navigate to table in Review
Comparison 2. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Maternal sepsis Show forest plot

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.37 [0.10, 56.41]

2.1.1 Elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

2.1.2 Non‐elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

2.1.3 Mixed type CS, or not defined

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.37 [0.10, 56.41]

2.2 Maternal endometritis Show forest plot

7

1161

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.76, 1.60]

2.2.1 Elective CS

1

122

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.05, 12.83]

2.2.2 Non‐elective CS

1

292

Risk Ratio (M‐H, Fixed, 95% CI)

1.72 [0.77, 3.84]

2.2.3 Mixed type CS, or not defined

5

747

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.61, 1.44]
Figures and Tables -
Comparison 2. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS
Navigate to table in Review
Comparison 3. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Maternal sepsis Show forest plot

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.37 [0.10, 56.41]

3.1.1 Cephalosporins C1 (1st generation) vs penicillins plus betalactamase inhibitors P2+

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

3.1.2 Cephalosporins C2 (2nd generation) vs penicillins plus betalactamase inhibitors P2+

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.37 [0.10, 56.41]

3.2 Maternal endometritis Show forest plot

7

1161

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.76, 1.60]

3.2.1 Cephalosporins C1 (1st generation) vs penicillins plus betalactamase inhibitors P2+

2

268

Risk Ratio (M‐H, Fixed, 95% CI)

1.56 [0.59, 4.16]

3.2.2 Cephalosporins C2 (2nd generation) vs penicillins plus betalactamase inhibitors P2+

6

893

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.68, 1.53]
Figures and Tables -
Comparison 3. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by generation of cephalosporin
Navigate to table in Review
Comparison 4. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 Maternal endometritis Show forest plot

6

2147

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.49, 1.66]

4.2 Sensitivity analysis (Fixed effects) Maternal endometritis Show forest plot

6

2147

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.86, 1.56]

4.3 Maternal fever (febrile morbidity) Show forest plot

5

798

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.39, 1.41]

4.4 Subgroup analysis by type of cephalosporin Maternal fever (febrile morbidity) Show forest plot

5

798

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.39, 1.41]

4.4.1 Cephalosporins C1 vs non‐antistaphylococcal penicillins P1 and P2

3

364

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.23, 0.97]

4.4.2 Cephalosporins C2 vs non‐antistaphylococcal penicillins P1 and P2

2

434

Risk Ratio (M‐H, Random, 95% CI)

1.24 [0.75, 2.05]

4.5 Maternal wound infection Show forest plot

5

915

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.59, 2.26]

4.6 Maternal urinary tract infection Show forest plot

4

515

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.59, 3.14]

4.7 Maternal composite adverse effects Show forest plot

2

1698

Risk Ratio (M‐H, Fixed, 95% CI)

2.02 [0.18, 21.96]

4.8 Maternal allergic reactions Show forest plot

2

329

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

4.9 Maternal length of hospital stay (days) Show forest plot

1

132

Mean Difference (IV, Fixed, 95% CI)

‐1.50 [‐2.46, ‐0.54]
Figures and Tables -
Comparison 4. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes
Navigate to table in Review
Comparison 5. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Maternal endometritis Show forest plot

6

2147

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.49, 1.66]

5.1.1 Elective CS

0

0

Risk Ratio (M‐H, Random, 95% CI)

Not estimable

5.1.2 Non‐elective CS

4

1818

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.99, 1.89]

5.1.3 Mixed type CS, or not defined

2

329

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.04, 2.21]
Figures and Tables -
Comparison 5. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS
Navigate to table in Review
Comparison 6. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by generation of cephalosporin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Maternal endometritis Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1.1 1st generation cephalosporins (C1) vs natural and broad spectrum penicillins (P1 and P2)

4

1036

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.33, 2.34]

6.1.2 2nd generation cephalosporins (C2) vs natural and broad spectrum penicillins (P1 and P2)

3

1111

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.72, 1.77]
Figures and Tables -
Comparison 6. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by generation of cephalosporin
Navigate to table in Review
Comparison 7. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Maternal endometritis Show forest plot

6

2147

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.49, 1.66]

7.1.1 1st and 2ndgeneration cephalosporins (C1 and C2) vs natural penicillins (P1)

0

0

Risk Ratio (M‐H, Random, 95% CI)

Not estimable

7.1.2 1st and 2ndgeneration cephalosporins (C1 and C2) vs broad spectrum penicillins (P2)

6

2147

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.49, 1.66]
Figures and Tables -
Comparison 7. Antistaphylococcal cephalosporins C1 and C2 (1st and 2nd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin
Navigate to table in Review
Comparison 8. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Maternal sepsis Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.2 Maternal endometritis Show forest plot

2

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.74 [1.10, 2.75]

8.3 Maternal fever (febrile morbidity) Show forest plot

1

114

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.29, 2.76]

8.4 Maternal wound infection Show forest plot

3

406

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.13, 1.28]

8.5 Maternal urinary tract infection Show forest plot

2

173

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.05, 5.75]

8.6 Maternal composite serious infectious complication Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.7 Maternal composite adverse effects Show forest plot

2

507

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.8 Maternal allergic reactions Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.9 Maternal nausea Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.10 Maternal vomiting Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.11 Maternal diarrhoea Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

8.12 Maternal skin rash Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 8. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ all outcomes
Navigate to table in Review
Comparison 9. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

9.1 Maternal sepsis Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

9.1.1 Elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

9.1.2 Non‐elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

9.1.3 Mixed type CS, or not defined

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

9.2 Maternal endometritis Show forest plot

2

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.74 [1.10, 2.75]

9.2.1 Elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

9.2.2 Non‐elective CS

2

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.74 [1.10, 2.75]

9.2.3 Mixed type CS, or not defined

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 9. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of CS
Navigate to table in Review
Comparison 10. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

10.1 Maternal sepsis Show forest plot

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

10.1.1 Cephalosporins C3 (3rd generation) vs penicillins P1 (natural)

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

10.1.2 Cephalosporins C3 (3rd generation) vs penicillins P2 (broad spectrum)

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

10.2 Maternal endometritis Show forest plot

2

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.74 [1.10, 2.75]

10.2.1 Cephalosporins C3 (3rd generation) vs penicillins P1 (natural)

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

10.2.2 Cephalosporins C3 (3rd generation) vs penicillins P2 (broad spectrum)

2

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.74 [1.10, 2.75]
Figures and Tables -
Comparison 10. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) ‐ subgrouped by type of penicillin
Navigate to table in Review
Comparison 11. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

11.1 Maternal endometritis Show forest plot

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.07, 15.88]

11.2 Maternal fever (febrile morbidity) Show forest plot

1

746

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.63, 2.22]

11.3 Maternal wound infection Show forest plot

2

865

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.10, 4.58]

11.4 Maternal urinary tract infection Show forest plot

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.05, 5.46]

11.5 Maternal composite serious infectious complication Show forest plot

1

746

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.6 Maternal composite adverse effects Show forest plot

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.7 Maternal allergic reactions Show forest plot

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.8 Maternal nausea Show forest plot

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.9 Maternal vomiting Show forest plot

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.10 Maternal diarrhoea Show forest plot

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.11 Maternal skin rash Show forest plot

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

11.12 Maternal length of hospital stay Show forest plot

1

746

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.10]
Figures and Tables -
Comparison 11. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ all outcomes
Navigate to table in Review
Comparison 12. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

12.1 Maternal endometritis Show forest plot

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.07, 15.88]

12.1.1 Elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

12.1.2 Non‐elective CS

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

12.1.3 Mixed type CS, or not defined

2

865

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.07, 15.88]
Figures and Tables -
Comparison 12. Minimally antistaphylococcal cephalosporins C3 (3rd generation) vs broad spectrum penicillins plus betalactamase inhibitors P2+ ‐ subgrouped by type of CS
Navigate to table in Review
Comparison 13. Other cephalosporin (only) regimens vs other penicillin (only) regimens

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

13.1 Maternal endometritis Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1.1 Cephalosporins C3 (3rd generation) vs penicillins P2 and P3 (broad spectrum and antistaphyloccal)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [0.18, 21.71]

13.2 Maternal fever (febrile morbidity) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.2.1 Cephalosporins C3 (3rd generation) vs penicillins P2 and P3 (broad spectrum and antistaphyloccal)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.41, 3.35]

13.3 Maternal wound infection Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.3.1 Cephalosporins C3 (3rd generation) vs penicillins P2 and P3 (broad spectrum and antistaphyloccal)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.05, 5.43]

13.4 Maternal vomiting Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.4.1 Cephalosporins C3 (3rd generation) vs penicillins P2 and P3 (broad spectrum and antistaphyloccal)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

7.00 [0.37, 133.78]

13.5 Maternal skin rash Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.5.1 Cephalosporins C3 (3rd generation) vs penicillins P2 and P3 (broad spectrum and antistaphyloccal)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

3.00 [0.12, 72.77]
Figures and Tables -
Comparison 13. Other cephalosporin (only) regimens vs other penicillin (only) regimens
Navigate to table in Review
Comparison 14. Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

14.1 Maternal sepsis Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.11, 60.57]

14.2 Maternal endometritis Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.68, 2.01]

14.3 Maternal wound infection Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

4.25 [0.21, 85.51]

14.4 Maternal urinary tract infection Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 1.69]
Figures and Tables -
Comparison 14. Fluoroquinolones F vs broad spectrum penicillin plus betalactamase inhibitors P2+
Navigate to table in Review
Comparison 15. Fluoroquinolones F vs cephalosporins C2 (2nd generation)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

15.1 Maternal sepsis Show forest plot

1

81

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.07, 16.63]

15.2 Maternal endometritis Show forest plot

1

81

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.76, 2.19]

15.3 Maternal wound infection Show forest plot

1

81

Risk Ratio (M‐H, Fixed, 95% CI)

2.15 [0.20, 22.82]

15.4 Maternal urinary tract infection Show forest plot

1

81

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 15. Fluoroquinolones F vs cephalosporins C2 (2nd generation)
Navigate to table in Review
Comparison 16. Carbapenems Ca vs cephalosporins C3 (3rd generation)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

16.1 Maternal endometritis Show forest plot

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.08, 17.82]

16.2 Maternal fever (febrile morbidity) Show forest plot

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.06, 6.09]

16.3 Maternal wound infection Show forest plot

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.02, 9.15]

16.4 Maternal urinary tract infection Show forest plot

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 16. Carbapenems Ca vs cephalosporins C3 (3rd generation)
Navigate to table in Review
Comparison 17. Macrolides M vs cephalosporins C1 (1st generation)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

17.1 Maternal fever (febrile morbidity) Show forest plot

1

70

Risk Ratio (M‐H, Fixed, 95% CI)

7.00 [0.37, 130.69]
Figures and Tables -
Comparison 17. Macrolides M vs cephalosporins C1 (1st generation)
Navigate to table in Review
Comparison 18. Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

18.1 Maternal endometritis Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.55, 2.10]

18.1.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

17.00 [0.99, 290.62]

18.2 Maternal fever (febrile morbidity) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.2.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.30, 2.46]

18.2.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

8.00 [1.89, 33.89]

18.3 Maternal wound infection Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.3.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.43, 3.03]

18.3.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

18.4 Maternal urinary tract infection Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.4.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.66, 2.82]

18.4.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

18.5 Maternal length of hospital stay (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

18.5.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐0.37, 0.15]

18.5.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

0

0

Mean Difference (IV, Fixed, 95% CI)

Not estimable

18.6 Costs Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

18.6.1 Broad spectrum penicillin P2 plus antistaphylococcal penicillin P3 plus aminoglycaside A plus nitroimadazole N vs cephalosporin C3 (3rd generation)

1

200

Mean Difference (IV, Fixed, 95% CI)

5.98 [4.28, 7.68]

18.6.2 Antistaphylococcal penicillin P3 plus aminoglycaside A vs cephalosporin C3 (3rd generation)

0

0

Mean Difference (IV, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 18. Other antibiotic regimens (multiple classes) vs cephalosporin (only) regimens
Navigate to table in Review
Comparison 19. Other antibiotic regimens (multiple classes) vs penicillin (only) regimens

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

19.1 Maternal endometritis Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.1.1 Lincosamide L plus aminoglycoside A vs natural penicillin P1

1

88

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.35, 6.15]

19.1.2 Cephalosporin C1 (1st generation) plus nitroimadazole vs broad spectrum penicillin P2

1

139

Risk Ratio (M‐H, Fixed, 95% CI)

2.70 [0.63, 11.55]

19.1.3 Cephalosporin C2 (2nd generation) plus nitroimadazole N vs broad spectrum penicillin plus betalactamase inhibitors P2+

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.77]

19.2 Maternal fever (febrile morbidity) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.2.1 Lincosamide L plus aminoglycoside A vs natural penicillin P1

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

19.2.2 Cephalosporin C1 (1st generation) plus nitroimadazole N vs broad spectrum penicillin P2

1

139

Risk Ratio (M‐H, Fixed, 95% CI)

2.36 [0.84, 6.62]

19.2.3 Cephalosporin C2 (2nd generation) plus nitroimadazole N vs broad spectrum penicillin plus betalactamase inhibitors P2+

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

2.93 [0.63, 13.68]

19.3 Maternal wound infection Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.3.1 Lincosamide L plus aminoglycoside A vs natural penicillin P1

1

88

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.16, 7.43]

19.3.2 Cephalosporin C1 (1st generation) plus nitroimadazole N vs broad spectrum penicillin P2

1

139

Risk Ratio (M‐H, Fixed, 95% CI)

2.02 [0.42, 9.63]

19.3.3 Cephalosporin C2 (2nd generation) plus nitroimadazole N vs broad spectrum penicillin plus betalactamase inhibitors P2+

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.06, 15.09]

19.4 Maternal urinary tract infection Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.4.1 Lincosamide L plus aminoglycoside A vs natural penicillin P1

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

19.4.2 Cephalosporin C1 (1st generation) plus nitroimadazole N vs broad spectrum penicillin P2

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

19.4.3 Cephalosporin C2 (2nd generation) plus nitroimadazole N vs broad spectrum penicillin plus betalactamase inhibitors P2+

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 19. Other antibiotic regimens (multiple classes) vs penicillin (only) regimens
Navigate to table in Review
Comparison 20. Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

20.1 Maternal sepsis Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.1.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

1

241

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.29, 2.26]

20.1.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.1.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

1

232

Risk Ratio (M‐H, Fixed, 95% CI)

3.21 [0.34, 30.45]

20.2 Maternal endometritis Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.2.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.2.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

156

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.2.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.3 Maternal fever (febrile morbidity) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.3.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.3.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.13, 4.14]

20.3.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

1

232

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.46, 3.27]

20.4 Maternal wound infection Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.4.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

1

241

Risk Ratio (M‐H, Fixed, 95% CI)

3.23 [0.34, 30.64]

20.4.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

2

256

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [0.19, 21.61]

20.4.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

1

232

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.40, 4.10]

20.5 Maternal urinary tract infection Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.5.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

1

241

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.07, 17.03]

20.5.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

156

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.5.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.6 Maternal composite adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.6.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.6.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.6.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

20.7 Maternal length of hospital stay Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

20.7.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

1

241

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.78, 0.18]

20.7.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

100

Mean Difference (IV, Fixed, 95% CI)

‐0.53 [‐1.36, 0.30]

20.7.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

0

0

Mean Difference (IV, Fixed, 95% CI)

Not estimable

20.8 Costs Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

20.8.1 Aminoglycoside A plus nitroimidazole N vs natural penicillin P1 plus nitroimidazole N plus macrolide M

0

0

Mean Difference (IV, Fixed, 95% CI)

Not estimable

20.8.2 Antistaphylococcal cephalosporin C1 and C2 (1st and 2nd generation) plus nitroimadazole N vs non‐antistaphylococcal penicillins P1 and P2 (natural and broad spectrum) plus nitroimadazole N

1

100

Mean Difference (IV, Fixed, 95% CI)

‐136.12 [‐165.73, ‐106.51]

20.8.3 Cephalosporin C3 (3rd generation) plus nitroimadazole N vs natural penicillin P1 plus broad spectrum penicillin P2 plus nitroimadazole N plus amphenicol Am

0

0

Mean Difference (IV, Fixed, 95% CI)

Not estimable
Figures and Tables -
Comparison 20. Other antibiotic regimens (multiple classes) versus different antibiotic regimens (multiple classes)
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Comparison 21. (Irrigation/lavage) cephalosporins vs penicillins

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

21.1 Maternal endometritis Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

21.1.1 Cephalosporins C2 (2nd generation) vs penicillins P2 (broad spectrum)

1

383

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.63, 1.43]

21.2 Maternal fever (febrile morbidity) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

21.2.1 Cephalosporins C2 (2nd generation) vs penicillins P2 (broad spectrum)

1

383

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.63, 1.43]

21.3 Maternal wound infection Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

21.3.1 Cephalosporins C2 (2nd generation) vs penicillins P2 (broad spectrum)

1

383

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.27, 4.17]
Figures and Tables -
Comparison 21. (Irrigation/lavage) cephalosporins vs penicillins
Navigate to table in Review