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Perioperative antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

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Abstract

Background

Solid organ transplant recipients are at high risk for infections due to the complexity of surgical procedures combined with the impact of immunosuppression. No consensus exists on the role of antibiotics for surgical site infections in solid organ transplant recipients.

Objectives

To assess the benefits and harms of prophylactic antimicrobial agents for preventing surgical site infections in solid organ transplant recipients.

Search methods

The Cochrane Kidney and Transplant Register of Studies was searched up to 21 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.

Selection criteria

All randomised controlled trials (RCTs) and quasi‐RCTs in any language assessing prophylactic antibiotics in preventing surgical site infections in solid organ transplant recipients at any time point after transplantation.

Data collection and analysis

Two authors independently determined study eligibility, assessed quality, and extracted data. Primary outcomes were surgical site infections and antimicrobial resistance. Other outcomes included urinary tract infections, pneumonias and septicaemia, death (any cause), graft loss, graft rejection, graft function, adverse reactions to antimicrobial agents, and outcomes identified by the Standardised Outcomes of Nephrology Group (SONG), specifically graft health, cardiovascular disease, cancer and life participation. Summary effect estimates were obtained using a random‐effects model and results were expressed as risk ratios (RR) and 95% confidence intervals (CI). The quality of the evidence was assessed using the risk of bias and the GRADE approach.

Main results

We identified eight eligible studies (718 randomised participants). Overall, five studies (248 randomised participants) compared antibiotics versus no antibiotics, and three studies (470 randomised participants) compared extended duration versus short duration antibiotics. Risk of bias was assessed as high for performance bias (eight studies), detection bias (eight studies) and attrition bias (two studies).

It is uncertain whether antibiotics reduce the incidence of surgical site infections as the certainty of the evidence has been assessed as very low (RR 0.42, 95% CI 0.21 to 0.85; 5 studies, 226 participants; I2 = 25%). The certainty of the evidence was very low for all other reported outcomes (death, graft loss, and other infections). It is uncertain whether extended duration antibiotics reduces the incidence of surgical site infections in either solid organ transplant recipients (RR 1.19, 95% CI 0.58 to 2.48; 2 studies, 302 participants; I2 = 0%) or kidney‐only transplant recipients (RR 0.50, 95% CI 0.05 to 5.48; 1 study, 205 participants) as the certainty of the evidence has been assessed as very low. The certainty of the evidence was very low for all other reported outcomes (death, graft loss, and other infections). None of the eight included studies evaluated antimicrobial agent adverse reactions, graft health, cardiovascular disease, cancer, life participation, biochemical and haematological parameters, intervention cost, hospitalisation length, or overall hospitalisation costs.

Authors' conclusions

Due to methodological limitations, risk of bias and significant heterogeneity, the current evidence for the use of prophylactic perioperative antibiotics in transplantation is of very low quality. Further high quality, adequately powered RCTs would help better inform clinical practice.

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.

Perioperative antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

What is the issue?
People receiving organ transplants are at high risk of infections due to the complex surgery and the weakening of the body’s immune defence against infection by anti‐rejection drugs. The germs causing infection around the time of transplantation may come from the person’s body, the transplanted organ, or the environment. Depending on the type of organ transplanted and the era in which the transplant took place, surgical site infections have been reported to occur following 3% to 53% of transplant operations. A surgical site infection is an infection that occurs after surgery in the part of the body where the surgery took place. This could include redness of the wound and/or a discharge of pus, which, if not treated with antibiotics or further surgery, could lead to bloodstream infection, infection of other organs in the body (including the transplant organ) or even death. Avoiding surgical site infection may improve patient and transplant survival. Giving antibiotics around the time of the transplant surgery may help to prevent surgical site infections but has not been studied in a systematic way. Giving antibiotics is also not without risk of harm since antibiotics are known to encourage the develop of antibiotic‐resistant germs, cause side effects like diarrhoea, and cost money.

What did we do?
We reviewed the literature up to April 2020, and found eight studies (718 randomised participants) that assessed whether antibiotics given around the time of transplant surgery prevent surgical site infections in organ transplant recipients.

What did we find?
When compared with no antibiotics, we are uncertain whether antibiotics reduce the occurrence of surgical site infections as the certainty of the evidence has been assessed as very low. When compared with short duration antibiotics, we are uncertain whether extended duration antibiotics reduce the occurrence of surgical site infections as the certainty of the evidence has been assessed as very low. Studies were limited by small size, short follow‐up duration, suboptimal methodological quality, and inconsistent reporting of outcomes. Consequently, the effects of antibiotics in preventing surgical site infections from occurring in people receiving organ transplant is uncertain.

Conclusions
It is uncertain whether antibiotics are beneficial in solid organ transplant recipients for the prevention of surgical site infections. We do not have enough data to estimate with precision some effects of antibiotics. A randomised controlled trial of antibiotic use versus placebo or single dose versus short course of antibiotic use is warranted.

Authors' conclusions

Implications for practice

  • Based on currently available data, there is very low certainty evidence to support routinely treating solid organ transplant recipients with antibiotics to prevent surgical site infections.

  • The extended duration antibiotic versus short duration antibiotic requires further exploration.

Implications for research

  • Further studies assessing the effects of extended duration antibiotics versus short duration antibiotics on surgical site infections would help inform practice. The current ongoing randomised study may help resolve existing uncertainties. However, different organism‐specific transplants need to be considered to provide better estimates to inform clinical practice.

  • Future appropriately powered studies are needed to examine the effects of perioperative antibiotics on surgical site infections, UTI, pneumonias and septicaemia, as well as the core outcomes identified by the SONG initiative (Tong 2018).

  • Future research should include information on both baseline level of antimicrobial resistance and change in drug resistance after antibiotic treatment, using appropriate samples (e.g. rectal swab and urine specimens) and systematic methodology.

Summary of findings

Open in table viewer
Summary of findings 1. Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Patient or population: solid organ transplant recipients
Intervention: antibiotics
Comparison: no antibiotics

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Risk with no antibiotics

Risk with antibiotics

Surgical site infections*

Time frame: 2 to 6 weeks

315 per 1,000

132 per 1,000
(66 to 268)

RR 0.42
(0.21 to 0.85)

226 (5)

⊕⊝⊝⊝
VERY LOW1,2,3

Death (any case)

Time frame: 2 to 4 weeks

128 per 1,000

35 per 1,000
(3 to 473)

RR 0.27
(0.02 to 3.69)

87 (2)

⊕⊝⊝⊝
VERY LOW1,2

Graft loss (including death with functioning graft)

Time frame: 2 weeks

37 per 1,000

0 per 1,000
(0 to 0)

RR 2.89
(0.12 to 67.96)

53 (1)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: UTI

Time frame: 2 to 6 weeks

619 per 1,000

545 per 1,000
(421 to 706)

RR 0.88
(0.68 to 1.14)

150 (3)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: septicaemia

Time frame: 2 to 6 weeks

93 per 1,000

47 per 1,000
(10 to 204)

RR 0.50
(0.11 to 2.19)

90 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: pneumonia

Time frame: up to 6 weeks

471 per 1,000

249 per 1,000
(99 to 621)

RR 0.53
(0.21 to 1.32)

37 (1)

⊕⊝⊝⊝
VERY LOW1,2

Adverse reactions

Not reported

Not reported

‐‐

‐‐

‐‐

*The risk in the intervention group (and its 95% CI) 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; UTI: urinary tract infection

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

*No studies attempted to blind participants, personnel, or data analysts. As surgical site infection assessment is partly subjective, we anticipated this would put the results at risk of being biased in favour of antibiotic treatment

1Imprecision (small number of study with participants)

2Study limitations (high risk of performance bias and detection bias)

3Moderate heterogeneity

Open in table viewer
Summary of findings 2. Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Patient or population: preventing post‐surgical site infections in solid organ transplant recipients
Intervention: extended duration antibiotics
Comparison: short duration antibiotics

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Risk with short duration antibiotics

Risk with extended duration antibiotics

Surgical site infections* (all)

Time frame: 30 days

73 per 1,000

87 per 1,000
(42 to 181)

RR 1.19
(0.58 to 2.48)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2,3

Surgical site infections: kidney transplant recipients

Time frame: 30 days

19 per 1,000

10 per 1,000
(1 to 106)

RR 0.50
(0.05 to 5.48)

205 (1)

⊕⊝⊝⊝
VERY LOW1,2

Surgical site infections: liver transplant recipients

Time frame: 30 days

188 per 1,000

246 per 1,000
(114 to 527)

RR 1.31
(0.61 to 2.81)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Death (any cause)

Time frame: 30 days

42 per 1,000

8 per 1,000
(0 to 166)

RR 0.20
(0.01 to 3.98)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Graft loss (including death with functioning graft)

Time frame: 30 days

93 per 1,000

92 per 1,000
(45 to 185)

RR 0.99
(0.49 to 2.00)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: UTI

Time frame: 30 days

125 per 1,000

61 per 1,000

(16 to 231)

RR 0.49

(0.13 to 1.85)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: septicaemia

Time frame: 30 days

146 per 1,000

131 per 1,000

(74 to 230)

RR 0.90

(0.51 to 1.58)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: pneumonia

Time frame: 30 days

No events

5/48**

RR 10.78

(0.61 to 189.77)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Adverse reactions

Not reported

Not reported

‐‐

‐‐

‐‐

*The risk in the intervention group (and its 95% CI) 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

*No studies attempted to blind participants, personnel, or data analysts. As surgical site infection assessment is partly subjective, we anticipated this would put the results at risk of being biased in favour of antibiotic treatment

** Event rate derived from the raw data. A 'per thousand' rate is non‐informative in view of the scarcity of evidence and zero events in the control group

1Imprecision (small number of study with participants)

2Study limitations (high risk of performance bias and detection bias)

3Moderate heterogeneity

Background

Description of the condition

Infections following solid organ transplantation are a leading cause of morbidity and death (Fishman 2017; Owens 2008). Depending on the organ transplanted and the era at which the transplant took place, surgical site infections have been reported to occur in 3% to 53% of patients transplanted (Choi 2013; Guaraldi 2005). A surgical site infection is an infection that occurs after surgery in the part of the body where the surgery took place. This could include simple erythema of the wound, with subsequent treatment, or return to theatre for wound debridement. The highest rates have been observed in small bowel/multivisceral transplants, where surgical site infection rates can reach over 90% when prosthetic mesh is used, followed by liver, pancreas, and kidney transplants (Choi 2013; Guaraldi 2005). Surgical site infections are associated with appreciable morbidity, and have been found to extend the average hospital stay by seven days, increase readmission rates, and increase the cost of hospitalisation by nearly 100% (Hollenbeak 2001; Kirkland 1999). Furthermore, surgical site infections have been associated with increased risks of graft failure and death in solid organ transplant recipients. Moreover, solid organ transplant recipients are at high risk of developing infections with antibiotic‐resistant organisms (Linares 2007; Patel 2008; Safdar 2002). Infections with multidrug‐resistant organisms have been associated with increased morbidity and death, particularly in solid organ transplant recipients (Linares 2007; Patel 2008). It is therefore crucial that strategies are developed to minimise surgical site infections following transplantation (Evertt 1994; Hellinger 2009; Humar 2001; Loinz 2006; Mattner 2007). The interventions and studies described need to be stratified based on time (era), patient type (organ) and examination of microbiological data.

Description of the intervention

Administration of one or more antibiotics either as a one‐off stat dose or extended for several days around the time of the operation may prevent surgical site infections from occurring following solid organ transplantation.

How the intervention might work

Antibiotics have commonly been prescribed prior to surgical procedures to try to mitigate the risk of surgical infections (Anesi 2018; Midtvedt 1998; Soave 2001). The principle is that time‐limited administration of antibiotics directed against most likely anticipated organisms in the perioperative period will prevent any resident or introduced micro‐organisms from developing an established surgical site infection. Although some transplant centres have used antibiotics prophylactically (Tillegard 1984; Townsend 1980) and some guidelines advocate for pre‐ or perioperative antibiotic prophylaxis (British Columbia Guidelines 2018; Princess Alexandra Hospital 2015), antibiotic use may be associated with significant harm including antibiotic‐associated diarrhoea, antibiotic resistance and increasing costs, and thus warrants further study.

Why it is important to do this review

There is uncertainty regarding the benefits versus harm in using prophylactic antibiotics as a potential strategy for preventing surgical site infections in solid organ transplant recipients (Bratzler 2013; Humar 2005). Specifically, there are no formal recommendations on using perioperative antibiotic prophylaxis in solid organ transplant recipients outside of the clinical practice guidelines for antimicrobial prophylaxis in surgery by the Infectious Diseases Society of America, American Society of Health‐System Pharmacists, Surgical Infection Society, and Society for Healthcare Epidemiology of America (IDSA/ASHP/SIS/SHEA). These provide general prophylactic antibiotic recommendations for solid organ transplant recipients, but do not address the unique circumstances of the transplant population (Bratzler 2013). Indeed, the transplant population is a vulnerable group given their increased risk of cardiovascular morbidity and death, and the higher infective risk compared with the general population (Bottomley 2013; Francis 2018).

With the high risk of surgical site infections in solid organ transplant recipients, and a rising incidence of multidrug‐resistant organisms in solid organ transplant donors and recipients, it seems logical to progressively broaden and extend perioperative antibiotic prophylaxis. However, the overuse of perioperative antibiotic prophylaxis may lead to a rise in the rates of Clostridium difficile colonization and colitis (Jobe 1995; Kreisel 1995; Privitera 1991), increase the rates of antimicrobial resistance (Roberts 1978) and increase adverse drug reactions as well as increase financial costs. Microbial colonisation patterns are also important in determining appropriate strategies. Consideration needs to be given to the amount and type of organism carried by the donor or the recipient at the clinical centre.
Given the complexities of solid organ transplant recipients and the unique risks for surgical site infections, guidance that is more customised to the solid organ transplant recipient scenario is needed. In the absence of formal guidelines, the aim of this study is to systematically review the evidence of perioperative antibiotics versus placebo or no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients.

Objectives

To assess the benefits and harms of prophylactic antimicrobial agents for preventing surgical site infections in solid organ transplant recipients.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) assessing the safety, efficacy, or both of perioperative antibiotics in surgical site infections in solid organ transplant recipients.

Types of participants

Inclusion criteria

  • Adults and children who receive a solid‐organ transplant, including combined grafts (e.g. kidney‐pancreas).

Exclusion criteria

  • Pregnant women.

Types of interventions

We included studies of any antibiotic medication. The following comparisons were investigated.

  • Any antibiotic medication versus placebo or no treatment

  • Any antibiotic medication versus any other antibiotic medication

  • Low dose versus high dose of the same antibiotic medication

  • Short‐course versus long‐course antibiotic therapy

  • Oral versus intravenous administration of the same or different antibiotic medication.

Types of outcome measures

The outcomes selected include the relevant SONG core outcome sets as specified by the Standardised Outcomes in Nephrology initiative (SONG 2017).

Primary outcomes

  • Surgical site infections

    • Stratification by era of study (multi‐drug resistance organisms and technical issues)

    • Microbiological data regarding resistance for surgical site infections.

Secondary outcomes

  • Death (any cause)

  • Graft loss (including death with a functioning graft)

  • Incidence of graft rejection at any time point (classified as clinically suspected and treated, or biopsy proven)

  • Antimicrobial resistance

  • Wound dehiscence/wound exploration

  • Other infections (e.g. urinary tract infections (UTI), pneumonia, bacteraemia)

  • Graft health

  • Cardiovascular disease

  • Cancer

  • Life participation

  • Biochemical and haematological parameters (e.g. C‐reactive protein, white cell count (WCC))

  • Adverse reactions to antibiotics

  • Length of hospitalisation

  • Cost of intervention and side‐effects

  • Overall hospitalisation cost.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Kidney and Transplant Register of Studies up to 21 April 2020 through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources.

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

  2. Weekly searches of MEDLINE OVID SP

  3. Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences

  4. Searching of the current year of EMBASE OVID SP

  5. Weekly current awareness alerts for selected kidney and transplant journals

  6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available on the Cochrane Kidney and Transplant website.

See Appendix 1 for search terms used in strategies for this review.

Searching other resources

  1. Reference lists of review articles, relevant studies, and clinical practice guidelines.

  2. Contacting relevant individuals/organisations seeking information about unpublished or incomplete studies.

  3. Grey literature sources (e.g. abstracts, dissertations, and theses), in addition to those already included in the Cochrane Kidney and Transplant Register of Studies, were not searched.

Data collection and analysis

Selection of studies

The search strategy described was used to obtain titles and abstracts of studies that were relevant to the review. The titles and abstracts were screened independently by two authors, who discarded studies that were not applicable, however studies and reviews that might include relevant data or information on studies were retained initially. Two authors independently assessed retrieved abstracts, and if necessary, the full text of these studies, to determine which studies satisfied the inclusion criteria. If there was a disagreement regarding the article validity and inclusion, a tie was broken by a third author.

Data extraction and management

Data extraction was carried out independently by two authors using standard data extraction forms. Studies reported in non‐English language journals were translated before assessment. Where more than one publication of one study existed, reports were grouped together and the publication with the most complete data was used in the analyses. Where relevant outcomes were only published in earlier versions, these data were used. Any discrepancy between published versions was highlighted.

Assessment of risk of bias in included studies

The following items was independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?

  • Was allocation adequately concealed (selection bias)?

  • Was knowledge of the allocated interventions adequately prevented during the study?

    • Participants and personnel (performance bias)

    • Outcome assessors (detection bias)

  • Were incomplete outcome data adequately addressed (attrition bias)?

  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

  • Was the study apparently free of other problems that could put it at a risk of bias?

Measures of treatment effect

For dichotomous outcomes (incidence of surgical site infection, death, graft loss, incidence of other infections, adverse reactions to antimicrobial agents), results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (biochemical parameters such as WCC, length of hospitalisation), the mean difference (MD) was used, or the standardised mean difference (SMD) if different scales were used.

Unit of analysis issues

  • Cluster RCTs: if cluster studies have been appropriately analysed to account for clustering in the data, direct measures of effect were extracted if available and used in the meta‐analyses using the generic inverse‐variance method. If such information was not available, we used cluster‐level data as individual units of analysis if the necessary data are available.

  • Cross‐over studies: we only used data from the first period if these were available.

  • Studies with multiple treatment groups: we tried to collapse multiple treatment groups into one where appropriate to enable single pair wise comparison (e.g. collapsing three groups of different doses of antibiotics into one group and include in single pair wise comparison versus placebo) (Higgins 2011).

Dealing with missing data

Any further information required from the original author was requested by written correspondence (e.g. emailing corresponding author/s) and any relevant information obtained in this manner was to be included in the review. Evaluation of important numerical data, such as screened, randomised patients as well as intention‐to‐treat, as‐treated and per‐protocol populations, was carefully performed. Attrition rates, for example due drop‐outs, losses to follow‐up and withdrawals, were investigated. Issues of missing data and imputation methods (e.g. last‐observation‐carried‐forward) were critically appraised (Higgins 2011).

Assessment of heterogeneity

We first assessed the heterogeneity by visual inspection of the forest plot. We quantified statistical heterogeneity using the I2 statistic, which described the percentage of total variation across studies that is due to heterogeneity rather than sampling error (Higgins 2003). A guide to the interpretation of I2 values was used as follows.

  • 0% to 40%: might not be important

  • 30% to 60%: may represent moderate heterogeneity

  • 50% to 90%: may represent substantial heterogeneity

  • 75% to 100%: considerable heterogeneity.

The importance of the observed value of I2 depends on the magnitude and direction of treatment effects and the strength of evidence for heterogeneity (e.g. P‐value from the Chi2 test, or a Cl for I2) (Higgins 2011).

Assessment of reporting biases

Funnel plots were to be used to assess for the potential existence of small study bias (Higgins 2011), however there were insufficient studies to do this.

Data synthesis

Data were pooled using the random‐effects model but the fixed‐effect model was also used to ensure robustness of the model chosen and susceptibility to outliers.

Subgroup analysis and investigation of heterogeneity

Subgroup analyses were planned to explore (if appropriate) possible sources of heterogeneity (participants, interventions, study quality). Heterogeneity among participants could be related to age, sex, time from transplantation to surgical site infections. Heterogeneity in treatments could be related to prior agent(s) used and the agent, dose, and duration of antibiotic therapy. Additionally, heterogeneity could be related to the type of organ transplant (e.g. kidney, liver, lung, pancreas, intestines), as well as the era of transplant (pre‐2000 versus post‐2000) and the country of origin of the studies. Heterogeneity among bacterial strains could be related to the following conditions.

  • Different antibiotics

  • Different doses

  • Transplant volume at each centre

  • Cost of intervention

  • Induction immunosuppression choice (e.g. anti‐thymocyte globulin versus basiliximab).

Adverse effects were tabulated and assessed with descriptive techniques, as they were likely to be different for the various agents used. Where possible, the risk difference with 95% CI was calculated for each adverse effect, either compared to no treatment or to another agent.

Sensitivity analysis

Sensitivity analyses were planned to explore the influence of the following factors on effect size.

  • Repeating the analysis excluding unpublished studies

  • Repeating the analysis taking account of risk of bias, as specified

  • Repeating the analysis excluding any very long or large studies to establish how much they dominate the results

  • Repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), and country.

There were insufficient studies to perform these sensitivity analyses.

'Summary of findings' tables

We have presented the main results of the review in 'Summary of findings' tables. These tables present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schunemann 2011a). The 'Summary of findings' tables also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (GRADE 2008; GRADE 2011). The GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schunemann 2011b). The following outcomes have been presented in the 'Summary of findings' tables.

  • Surgical site infection

    • Stratification by era of study (multi‐drug resistance organisms and technical issues)

    • Microbiological data regarding resistance for surgical site infection

  • Death (any cause)

  • Graft loss including death with a functioning graft

  • Other infections (e.g. UTI, pneumonia, bacteraemia)

  • Adverse reactions to antibiotics

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

We searched the Specialised Register and identified 16 reports. After screening, eight studies (12 reports) were included and three studies (three reports) were excluded. One ongoing study was identified (2007‐004284‐21). This study and will be assessed in a future update of this review (Figure 1).


Study flow diagram.

Study flow diagram.

Included studies

Eight studies (718 randomised participants) were included in this review (Berry 2019; Cohen 1988; Evans 1988; Nikeghbalian 2010; Orlando 2015; Robles 1990; Townsend 1980; Wilms 1986).

Five studies (248 randomised participants) examined the effect of antibiotics versus no antibiotics in the prevention of surgical site infection in solid organ transplant recipients (Cohen 1988; Evans 1988; Robles 1990; Townsend 1980; Wilms 1986). The antibiotics administered were cefuroxime and piperacillin/tazobactam (Cohen 1988), amoxicillin and clavulanic acid (Evans 1988), cefamandole and tobramycin (Townsend 1980), either ceftriaxone or cefotaxime (Robles 1990), or cephalosporin (actual therapy not specified) (Wilms 1986).

Three studies (470 randomised participants) examined the effect of extended antibiotics versus short course antibiotics in the prevention of surgical site infections in solid‐organ transplant recipients (Berry 2019; Nikeghbalian 2010; Orlando 2015). The intervention versus control arms were cefazolin every 12 hours or cefotaxime every 12 hours for three or five days, respectively, versus a single dose of cefazolin (Orlando 2015), three‐day course of piperacillin/tazobactam every eight hours versus single dose of piperacillin/ tazobactam (Berry 2019), and ceftriaxone and metronidazole versus ampicillin/sulbactam and cefazolin, although the duration of either therapy arms was not specified (Nikeghbalian 2010).

Excluded studies

Three studies were excluded from this review (Hirokawa 2013; Moreno 1997; Salmela 1990). The reason for exclusion was because of the wrong study population: examining patients with liver resection rather than liver transplantation (Hirokawa 2013); efficacy of antimicrobial therapy upon presentation with a fever 30 days following kidney transplant (Moreno 1997);, or the wrong study outcome (i.e. not assessing surgical site infection (Salmela 1990).

Risk of bias in included studies

Risks of bias in domains of individual studies are presented in Figure 2 and the summary of risk of bias of all the included studies is presented in Figure 3.


Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.


Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation

Random sequence generation was judged to be low risk in two studies (Berry 2019; Orlando 2015). The risk of bias was unclear in the remaining six studies.

Allocation concealment

Allocation concealment was judged to be low risk in one study (Berry 2019). The risk of bias was unclear in the remaining seven studies.

Blinding

Performance bias (blinding of participants) was judged to be of high risk in all eight studies. Detection bias (blinding of outcomes assessor) was judged to be high risk in all eight studies.

Incomplete outcome data

Attrition bias was judged to be of low risk in five studies (Cohen 1988; Evans 1988; Berry 2019; Orlando 2015; Robles 1990; Townsend 1980) and at high risk in one studies (Wilms 1986). The risk of bias was unclear in one study (Nikeghbalian 2010).

Selective reporting

The risk of bias was unclear in all eight studies.

Other potential sources of bias

All studies were identified as low risk for other potential sources of bias. The risk of sponsorship bias was considered low due to the nature of the research question.

Effects of interventions

See: Summary of findings 1 Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients; Summary of findings 2 Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Antibiotics versus no antibiotics

See summary of findings Table 1 (antibiotics versus no treatment for preventing surgical site infection in solid organ transplant recipients)

Surgical site infections

It is uncertain whether antibiotics reduce the incidence of surgical site infection (RR 0.42, 95% CI 0.21 to 0.85; 5 studies, 226 participants; I2 = 25%) as the certainty of the evidence has been assessed as very low (Analysis 1.1).

Microbiological data regarding resistance for surgical site infections

Cohen 1988 reported four antibiotic‐resistant isolates, two Klebsiella and two Enterobacter, were cultured from infected surgical sites in kidney transplant recipients who received both cefuroxime and piperacillin/tazobactam.

Death (any cause)

It is uncertain whether antibiotics reduce the incidence of overall death because the certainty of the evidence has been assessed as very low (RR 0.27, 95% CI 0.02 to 3.69; 2 studies, 87 participants; I2 = 43%) (Analysis 1.2).

Graft loss including death with functioning graft

It is uncertain whether antibiotics reduce the incidence of graft loss including death with functioning graft because the certainty of the evidence from one study (Cohen 1988) has been assessed as very low (RR 2.89, 95% CI 0.12 to 67.96; 53 participants) (Analysis 1.3).

Other infections

It is uncertain whether antibiotics reduce the incidence of UTIs because the certainty of the evidence has been assessed as very low (RR 0.88, 95% CI 0.68 to 1.14; 3 studies, 150 participants; I2 = 0%) (Analysis 1.4).

It is uncertain whether antibiotics reduce the incidence of septicaemia because the certainty of the evidence has been assessed as very low (RR 0.50, 95% CI 0.11 to 2.19; 2 studies, 90 participants; I2 = 0%) (Analysis 1.5).

It is uncertain whether antibiotics reduce the incidence of pneumonia because the certainty of the evidence from one study (Townsend 1980) has been assessed as very low (RR 0.53, 95% CI 0.21 to 1.32; 37 participants) (Analysis 1.6).

Extended duration versus short duration antibiotics

See summary of findings Table 2 (extended versus short duration antibiotics for preventing surgical site infection in solid organ transplant recipients)

Surgical site infections

It is uncertain whether extended duration antibiotics reduces the incidence of surgical site infection because the certainty of the evidence has been assessed as very low (RR 1.19, 95% CI 0.58 to 2.48; 2 studies, 302 participants; I2 = 0%) (Analysis 2.1). It is uncertain whether extended duration antibiotics reduces the incidence of surgical site infections in kidney only transplant recipients because the certainty of the evidence from one study (Orlando 2015) has been assessed as very low (RR 0.50, 95% CI 0.05 to 5.48; 205 participants) (Analysis 2.1.1). It is uncertain whether extended duration antibiotics reduces the incidence of surgical site infections in liver only transplant recipients because the certainty of the evidence from one study (Berry 2019) has been assessed as very low (RR 1.34, 95% CI 0.61 to 2.81; 97 participants) (Analysis 2.1.2).

Microbiological data regarding resistance for surgical site infections

Five cases of vancomycin‐resistant enterococci were found intra‐abdominally in liver transplant recipients receiving three days of piperacillin/tazobactam compared with one case of vancomycin‐resistant enterococci found both intra‐abdominally and in blood in a liver transplant recipient receiving a stat dose of piperacillin/tazobactam (Berry 2019). These recipients may already have had vancomycin‐resistant enterococci pre‐transplant, but this is difficult to ascertain whether resistant organisms were attributed to the use of pre‐transplant antibiotics.

Death (any cause)

It is uncertain whether extended duration antibiotics reduces the incidence of death because the certainty of the evidence from one study (Berry 2019) has been assessed as very low (RR 0.20, 95% CI 0.01 to 3.98; 97 participants) (Analysis 2.2).

Incidence of graft loss including death with functioning graft

It is uncertain whether extended duration antibiotics reduces the incidence of graft loss including death with functioning graft because the certainty of the evidence has been assessed as very low (RR 0.99, 95% CI 0.49 to 2.00; 2 studies, 302 participants; I2 = 0%) (Analysis 2.3).

Other infections

It is uncertain whether extended duration antibiotics reduces the incidence of UTI because the certainty of the evidence from one study (Berry 2019) has been assessed as very low (RR 0.49, 95%CI 0.13 to 1.85; 97 participants) (Analysis 2.4).

It is uncertain whether extended duration antibiotics reduces the incidence of septicaemia because the certainty of the evidence has been assessed as very low (RR 0.90, 95% CI 0.51 to 1.58; 2 studies, 302 participants; I2 = 0%) (Analysis 2.5).

It is uncertain whether extended duration antibiotics reduces the incidence of pneumonia because the certainty of the evidence from one study (Berry 2019) has been assessed as very low (RR 10.78, 95% CI 0.61 to 189.77; 97 participants) (Analysis 2.6).

Wound exploration

It is uncertain whether extended duration antibiotics reduces the incidence of wound exploration because the certainty of the evidence from one study (Orlando 2015) has been assessed as very low (RR 0.40, 95% CI 0.08 to 2.03; 205 participants) (Analysis 2.7).

Other outcomes

None of the eight included studies evaluated or reported antimicrobial agent adverse reactions, graft health, cardiovascular disease, cancer, life participation, biochemical parameters, haematological parameters, length of hospitalisation, transplant volume at each centre, cost of intervention or overall hospitalisation costs. Additional information was requested from the authors of the eight studies but was not provided.

Discussion

Summary of main results

This systematic review has shown that there is insufficient quality evidence to conclude with certainty that antibiotics reduce the incidence of surgical site infections. In the eight included studies, the results had a high degree of heterogeneity, a high risk of bias, and suboptimal methodological design, specifically many single studies, inconsistent comparisons with variable outcome measures (non‐patient relevant), and limited data on harms including antibiotic resistance. None of the core outcomes defined by the SONG initiative were reported in any of the eight included studies (Tong 2018). Given the limitations of the available evidence, we were not able to explore and precisely estimate potential complications arising from perioperative antibiotic use.

Overall completeness and applicability of evidence

Overall, it is difficult to apply the evidence gained from this Cochrane review to clinical practice. First, the included RCTs examined outcomes in kidney and liver transplant recipients, such that the results may not be generalisable to other solid organ transplants, which may have different risks of perioperative infection. In particular, multivisceral transplant patients may be at appreciably higher risk of infections and perioperative antibiotics of longer duration may be required. Second, of the eight included studies, five were published prior to the year 2000 and so may not be applicable to contemporary transplant practice which has seen significant changes in recipient and donor selection, immunosuppressive regimens, infection control practices, and micro‐organism resistance patterns and pathogenicity. Third, none of the eight included studies considered the possibility of donor infection/colonisation in guiding antimicrobial management. For example, a study performed in lung transplant recipients found that positive donor bronchoalveolar lavage cultures were associated with longer intensive care unit stays and decreased survival post‐transplantation (Roberts 1978). Fourth, only three of the eight included studies reported the resistance patterns of micro‐organisms to antimicrobial therapy. This is an important consideration because colonisation may increase the incidence of surgical site infections as noted in heart and lung (Avlonitis 2003), liver (Russell 2008), and kidney (Pouch 2015) transplant recipients. Fifth, the variable, non‐standardised definitions of surgical site infections used by the eight studies may lead to misclassification bias. The detection of a surgical site infections depends considerably on how aggressively clinicians investigate them. Surgical site infections are often found post‐discharge and are treated in the community, and thus may not detected in the hospital environment.

Quality of the evidence

The quality of the existing evidence was limited by suboptimal methodological design, specifically a failure to specify methods of randomisation and allocation concealment. In addition, a considerable number of studies had high risks of performance and detection biases. In general, studies were limited by small sample size and an unclear duration of follow‐up, which reduced the strength of the review. These limitations suggest that additional studies are likely to change our confidence in the effect estimates (GRADE 2008).

Potential biases in the review process

The strength of this review is that it included an up‐to‐date and comprehensive systematic review of previous publications through a thorough MEDLINE, EMBASE and CENTRAL search and included only RCTs or quasi‐RCTs, as pre‐specified. None of the authors had any commercial conflict of interest related to this review, and although every care was taken to interpret the data as objectively as possible, it is difficult to rule out a subconscious intellectual conflict that may have influenced the conclusions.

Agreements and disagreements with other studies or reviews

This systematic review has demonstrated that it is uncertain whether antibiotics reduce the incidence of surgical site infections because the certainty of the evidence has been assessed as very low. To the best of our knowledge, there are no published guidelines relating to the use of perioperative antibiotics in solid organ transplant recipients, although there are published recommendations which relate to the general population who are not immunocompromised which also provide some general recommendations for perioperative antibiotic prophylaxis in heart (level A), lung (level A), liver (level B), kidney (level A) and kidney‐pancreas (level A) transplantation but not small bowel/ multivisceral transplantation (Bratzler 2013).

Study flow diagram.

Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1: Antibiotics versus no antibiotics, Outcome 1: Surgical site infections

Figures and Tables -
Analysis 1.1

Comparison 1: Antibiotics versus no antibiotics, Outcome 1: Surgical site infections

Comparison 1: Antibiotics versus no antibiotics, Outcome 2: Death (any cause)

Figures and Tables -
Analysis 1.2

Comparison 1: Antibiotics versus no antibiotics, Outcome 2: Death (any cause)

Comparison 1: Antibiotics versus no antibiotics, Outcome 3: Graft loss (including death with functioning graft)

Figures and Tables -
Analysis 1.3

Comparison 1: Antibiotics versus no antibiotics, Outcome 3: Graft loss (including death with functioning graft)

Comparison 1: Antibiotics versus no antibiotics, Outcome 4: Urinary tract infection

Figures and Tables -
Analysis 1.4

Comparison 1: Antibiotics versus no antibiotics, Outcome 4: Urinary tract infection

Comparison 1: Antibiotics versus no antibiotics, Outcome 5: Septicaemia

Figures and Tables -
Analysis 1.5

Comparison 1: Antibiotics versus no antibiotics, Outcome 5: Septicaemia

Comparison 1: Antibiotics versus no antibiotics, Outcome 6: Pneumonia

Figures and Tables -
Analysis 1.6

Comparison 1: Antibiotics versus no antibiotics, Outcome 6: Pneumonia

Comparison 2: Extended duration versus short duration antibiotics, Outcome 1: Surgical site infections

Figures and Tables -
Analysis 2.1

Comparison 2: Extended duration versus short duration antibiotics, Outcome 1: Surgical site infections

Comparison 2: Extended duration versus short duration antibiotics, Outcome 2: Death (any cause)

Figures and Tables -
Analysis 2.2

Comparison 2: Extended duration versus short duration antibiotics, Outcome 2: Death (any cause)

Comparison 2: Extended duration versus short duration antibiotics, Outcome 3: Graft loss (including death with functioning graft)

Figures and Tables -
Analysis 2.3

Comparison 2: Extended duration versus short duration antibiotics, Outcome 3: Graft loss (including death with functioning graft)

Comparison 2: Extended duration versus short duration antibiotics, Outcome 4: Urinary tract infection

Figures and Tables -
Analysis 2.4

Comparison 2: Extended duration versus short duration antibiotics, Outcome 4: Urinary tract infection

Comparison 2: Extended duration versus short duration antibiotics, Outcome 5: Septicaemia

Figures and Tables -
Analysis 2.5

Comparison 2: Extended duration versus short duration antibiotics, Outcome 5: Septicaemia

Comparison 2: Extended duration versus short duration antibiotics, Outcome 6: Pneumonia

Figures and Tables -
Analysis 2.6

Comparison 2: Extended duration versus short duration antibiotics, Outcome 6: Pneumonia

Comparison 2: Extended duration versus short duration antibiotics, Outcome 7: Wound exploration

Figures and Tables -
Analysis 2.7

Comparison 2: Extended duration versus short duration antibiotics, Outcome 7: Wound exploration

Summary of findings 1. Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Patient or population: solid organ transplant recipients
Intervention: antibiotics
Comparison: no antibiotics

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Risk with no antibiotics

Risk with antibiotics

Surgical site infections*

Time frame: 2 to 6 weeks

315 per 1,000

132 per 1,000
(66 to 268)

RR 0.42
(0.21 to 0.85)

226 (5)

⊕⊝⊝⊝
VERY LOW1,2,3

Death (any case)

Time frame: 2 to 4 weeks

128 per 1,000

35 per 1,000
(3 to 473)

RR 0.27
(0.02 to 3.69)

87 (2)

⊕⊝⊝⊝
VERY LOW1,2

Graft loss (including death with functioning graft)

Time frame: 2 weeks

37 per 1,000

0 per 1,000
(0 to 0)

RR 2.89
(0.12 to 67.96)

53 (1)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: UTI

Time frame: 2 to 6 weeks

619 per 1,000

545 per 1,000
(421 to 706)

RR 0.88
(0.68 to 1.14)

150 (3)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: septicaemia

Time frame: 2 to 6 weeks

93 per 1,000

47 per 1,000
(10 to 204)

RR 0.50
(0.11 to 2.19)

90 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: pneumonia

Time frame: up to 6 weeks

471 per 1,000

249 per 1,000
(99 to 621)

RR 0.53
(0.21 to 1.32)

37 (1)

⊕⊝⊝⊝
VERY LOW1,2

Adverse reactions

Not reported

Not reported

‐‐

‐‐

‐‐

*The risk in the intervention group (and its 95% CI) 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; UTI: urinary tract infection

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

*No studies attempted to blind participants, personnel, or data analysts. As surgical site infection assessment is partly subjective, we anticipated this would put the results at risk of being biased in favour of antibiotic treatment

1Imprecision (small number of study with participants)

2Study limitations (high risk of performance bias and detection bias)

3Moderate heterogeneity

Figures and Tables -
Summary of findings 1. Antibiotics versus no antibiotics for preventing post‐surgical site infections in solid organ transplant recipients
Summary of findings 2. Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients

Patient or population: preventing post‐surgical site infections in solid organ transplant recipients
Intervention: extended duration antibiotics
Comparison: short duration antibiotics

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Risk with short duration antibiotics

Risk with extended duration antibiotics

Surgical site infections* (all)

Time frame: 30 days

73 per 1,000

87 per 1,000
(42 to 181)

RR 1.19
(0.58 to 2.48)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2,3

Surgical site infections: kidney transplant recipients

Time frame: 30 days

19 per 1,000

10 per 1,000
(1 to 106)

RR 0.50
(0.05 to 5.48)

205 (1)

⊕⊝⊝⊝
VERY LOW1,2

Surgical site infections: liver transplant recipients

Time frame: 30 days

188 per 1,000

246 per 1,000
(114 to 527)

RR 1.31
(0.61 to 2.81)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Death (any cause)

Time frame: 30 days

42 per 1,000

8 per 1,000
(0 to 166)

RR 0.20
(0.01 to 3.98)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Graft loss (including death with functioning graft)

Time frame: 30 days

93 per 1,000

92 per 1,000
(45 to 185)

RR 0.99
(0.49 to 2.00)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: UTI

Time frame: 30 days

125 per 1,000

61 per 1,000

(16 to 231)

RR 0.49

(0.13 to 1.85)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: septicaemia

Time frame: 30 days

146 per 1,000

131 per 1,000

(74 to 230)

RR 0.90

(0.51 to 1.58)

302 (2)

⊕⊝⊝⊝
VERY LOW1,2

Other infection: pneumonia

Time frame: 30 days

No events

5/48**

RR 10.78

(0.61 to 189.77)

97 (1)

⊕⊝⊝⊝
VERY LOW1,2

Adverse reactions

Not reported

Not reported

‐‐

‐‐

‐‐

*The risk in the intervention group (and its 95% CI) 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

*No studies attempted to blind participants, personnel, or data analysts. As surgical site infection assessment is partly subjective, we anticipated this would put the results at risk of being biased in favour of antibiotic treatment

** Event rate derived from the raw data. A 'per thousand' rate is non‐informative in view of the scarcity of evidence and zero events in the control group

1Imprecision (small number of study with participants)

2Study limitations (high risk of performance bias and detection bias)

3Moderate heterogeneity

Figures and Tables -
Summary of findings 2. Extended versus short duration antibiotics for preventing post‐surgical site infections in solid organ transplant recipients
Comparison 1. Antibiotics versus no antibiotics

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Surgical site infections Show forest plot

5

226

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.21, 0.85]

1.2 Death (any cause) Show forest plot

2

87

Risk Ratio (M‐H, Random, 95% CI)

0.27 [0.02, 3.69]

1.3 Graft loss (including death with functioning graft) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

1.4 Urinary tract infection Show forest plot

3

150

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.68, 1.14]

1.5 Septicaemia Show forest plot

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.11, 2.19]

1.6 Pneumonia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 1. Antibiotics versus no antibiotics
Comparison 2. Extended duration versus short duration antibiotics

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Surgical site infections Show forest plot

2

302

Risk Ratio (M‐H, Random, 95% CI)

1.19 [0.58, 2.48]

2.1.1 Kidney transplant recipients

1

205

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.05, 5.48]

2.1.2 Liver transplant recipients

1

97

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.61, 2.81]

2.2 Death (any cause) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2.3 Graft loss (including death with functioning graft) Show forest plot

2

302

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.49, 2.00]

2.4 Urinary tract infection Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2.5 Septicaemia Show forest plot

2

302

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.51, 1.58]

2.6 Pneumonia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2.7 Wound exploration Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 2. Extended duration versus short duration antibiotics