Review
Risk factors for infection and/or colonisation with extended-spectrum β-lactamase-producing bacteria in the neonatal intensive care unit: a meta-analysis

https://doi.org/10.1016/j.ijantimicag.2017.06.027Get rights and content

Highlights

  • Empirical antibiotic use for infections is placing significant selective pressure on resistant bacteria.

  • Invasive procedures and antibiotic treatment are risks for ESBL-producing bacterial infection.

  • Theoretical basis for preventive measures and targeted interventions in ESBL-producing bacterial infections.

Abstract

Extended-spectrum β-lactamase (ESBL)-producing bacteria are an important cause of healthcare-associated infections in the neonatal intensive care unit (NICU). The aim of this meta-analysis was to identify risk factors associated with infection and/or colonisation with ESBL-producing bacteria in the NICU. Electronic databases were searched for relevant studies published from 1 January 2000 to 1 July 2016. The literature was screened and data were extracted according to the inclusion and exclusion criteria. The Z-test was used to calculate the pooled odds ratio (OR) of the risk factors. ORs and their 95% confidence intervals were used to determine the significance of the risk. A total of 14 studies, including 746 cases and 1257 controls, were identified. Thirteen risk factors were determined to be related to infection and/or colonisation with ESBL-producing bacteria in the NICU: birthweight [standardised mean difference (SMD) = 1.17]; gestational age (SMD = 1.36); Caesarean delivery (OR = 1.76); parenteral nutrition (OR = 7.51); length of stay in the NICU (SMD = 0.72); mechanical ventilation (OR = 4.8); central venous catheter use (OR = 2.85); continuous positive airway pressure (OR = 5.0); endotracheal intubation (OR = 2.82); malformations (OR = 2.89); previous antibiotic use (OR = 6.72); ampicillin/gentamicin (OR = 2.31); and cephalosporins (OR = 6.0). This study identified risk factors for infection and/or colonisation with ESBL-producing bacteria in the NICU, which may provide a theoretical basis for preventive measures and targeted interventions.

Introduction

Neonates have recently been reported as a high-risk population for healthcare-associated infections (HCAIs) [1]. These infections are responsible for significant mortality and subsequent morbidity in the neonatal intensive care unit (NICU) [2]. The high incidence of bloodstream infections in neonates (0–28 days) leads to an increasing use of antibiotics [3], [4]. Owing to the high antibiotic pressure in the hospital environment, infection and/or colonisation with multidrug-resistant Gram-negative bacilli, in particular Klebsiella pneumoniae producing extended-spectrum β-lactamase (ESBL) enzymes, has been reported with increasing frequency in the NICU [5], [6].

Since ESBL-producing K. pneumoniae (ESBL-KP) was first isolated in Germany in 1983 [7], ESBL-producing bacteria have spread rapidly on a global scale, probably because of the extensive use of third-generation cephalosporins [8], [9]. ESBLs are enzymes produced by certain bacteria that can deactivate several antibiotics by hydrolysing the amide bond in the β-lactam ring of these antibiotics. The spectrum of enzyme activity towards penicillins, aztreonam and extended-spectrum cephalosporins such as ceftazidime, cefotaxime and ceftriaxone is extended because of mutations in the gene encoding ESBLs [10].

A previous study reported that the overall gastrointestinal colonisation rate of ESBL-producing Enterobacteriaceae (ESBL-E) in hospitalised patients is up to 52%, among which faecal ESBL-E carriage rates in neonates, children and adults were 74%, 59% and 46%, respectively [11]. Compared with adults, infection outbreaks of with multidrug-resistant ESBL-E in neonatal units with a high mortality rate (45%) have been reported [12].

In response to the growing trend of HCAIs caused by ESBL-producing bacteria in the NICU, determining risk factors for infection and/or colonisation for adoption of preventive strategies is important [13], [14]. To date, infections caused by ESBL-producing bacteria in adult and paediatric intensive care units have been well described [15], [16], [17]. However, clinical data regarding neonates in the NICU, particularly with respect to risk factors for infection and/or colonisation, are limited. The reported outcomes of previous studies regarding risk factors for infection and/or colonisation were inconsistent. To resolve these conflicting results, a larger sample size characteristic of meta-analyses is needed. Therefore, this meta-analysis was performed with the aim of identifying risk factors associated with infection and/or colonisation of ESBL-producing bacteria in the NICU.

Section snippets

Data search and screening strategy

Electronic databases were searched for relevant studies published from 1 January 2000 to 1 July 2016. All literature related to risk factors for infection and/or colonisation with ESBL-producing bacteria in the NICU were identified via a systematic search (English and Chinese languages) in PubMed, Web of Science, EBSCO, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM), China Science and Technology Journal

Literature search

A total of 168 potentially relevant references were systematically identified through searching the electronic databases; 62 duplicate studies were excluded. After screening of the titles and abstracts, 81 studies were not relevant to risk factors for infection and/or colonisation with ESBL-producing bacteria in the NICU; thus, 25 studies underwent full-text review. Among these studies, 11 studies were excluded because they failed to match the inclusion criteria or were reviews and reports.

Discussion

HCAIs caused by ESBL-producing bacteria are a growing concern in the NICU [11]. ESBL-producing bacteria, which are resistant to multiple antibiotics, are a potential important cause of HCAI outbreaks, and identifying risk factors for infection and/or colonisation with ESBL-producing bacteria in the NICU is critical [32]. Although the development of infection/colonisation is associated with the same risk factors as other healthcare-related infections, including low birthweight, premature,

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