|Prophylactic antibiotics in the prevention of catheter-associated bloodstream bacterial infection in preterm neonates: a systematic review
|Lodha A, Furlan AD, Whyte H, Moore AM
The review concluded that prophylactic vancomycin appeared to be effective in preventing catheter-related sepsis in pre-term newborn babies, but the risk of bacterial resistance needs further evaluation. Given the small number of included trials and the small sample sizes, the pooled results may not be robust, so caution is warranted when interpreting the authors’ conclusions.
To determine the effectiveness of prophylactic antibiotics for the prevention of catheter-related (central venous line) blood stream infections in pre-term neonates.
MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to July 2007 for articles in any language. Search terms were reported. The Annual Meetings of the Paediatric Academic Society and the Canadian Paediatric Society were searched from 1990 to July 2007. Citation tracking was used and experts in the field were also contacted.
Randomised controlled trials (RCTs) in catheterised (centrally or peripherally central venous catheters) pre-term (less than 37 weeks) neonates (less than one-month old), admitted to neonatal intensive care units and treated with prophylactic antibiotics for the prevention for catheter-related blood stream infections, were eligible for inclusion. Trials had to report on sepsis as measured by true catheter-related blood stream infection or probable catheter-related blood stream infection (primary outcome). Trials in neonates with renal disease or congenital malformations were excluded, as were trials in neonates in which the catheter was inserted within 48 hours after birth.
The included trials evaluated neonates treated with vancomycin (25μgml-1) or amoxicillin (100mg/kg/day) versus control for the prevention of catheter-related blood stream infections after catheter insertion. Vancomycin was given with or without heparin or total parental nutrition. Control interventions included heparin or normal saline, no antibiotics, or total parental nutrition alone. The primary outcome was sepsis, but vancomycin resistance, death, necrotising enterocolitis, and adverse events were also reported.
Two reviewers independently performed study selection, and disagreements were resolved by consensus or consultation with a third reviewer if needed.
Assessment of study quality
Two reviewers independently assessed trial quality using the van Tulder criteria, which assessed 11 quality factors. Trials scoring at least 6 out of 11 were deemed high quality.
Two reviewers independently extracted data on the incidence of sepsis to calculate relative risks (RRs) and 95% confidence intervals (CIs). For secondary outcomes, continuous outcomes (catheter duration) were extracted to calculate weighted mean differences (WMDs), while dichotomous data were extracted to calculate absolute risk reductions (ARRs), and RRs. Trial authors were contacted for missing data.
Methods of synthesis
The pooled relative risks, weighted mean differences, and absolute risk reductions were combined in a fixed-effects meta-analysis. Trials were grouped by type of antibiotic. Statistical heterogeneity was assessed using X2 and I2 statistics. Publication bias was assessed by funnel plot assessment. The number needed to treat (NNT) was also calculated.
Results of the review
Three RCTs (n=317 neonates enrolled) were included in the review: two trials of vancomycin (n=169 enrolled) and one trial of amoxicillin (n=148). The two vancomycin trials scored 11 out of 11 and were deemed high quality; the one amoxicillin trial scored 4 out of 11 and was deemed low quality.
Vancomycin: Compared with control, neonates who received vancomycin had a statistically significant 87% reduction in the incidence of sepsis (RR 0.13, 95% CI 0.04 to 0.46; I2=0%; NNT 5) and a statistically significant decrease in the risk of infection (ARR –0.2, 95% CI –0.29 to –0.11). There was no difference in the total duration of catheter stay, mortality, or positive culture results. There was no evidence of publication bias.
Amoxicillin: Compared with control, neonates who received amoxicillin did not have a statistically significant difference in the incidence of sepsis (RR 0.40, 95% CI 0.12 to 1.35). There was a statistically significant difference in the rate of colonisation, with higher rates in the control group (RR 0.48, 95% CI 0.24 to 0.95). Amoxicillin reduced the risk of infection (ARR -0.03%, -0.08 to -0.01), while there were no differences in the duration of catheterisation between treatment groups. No serious side effects due to amoxicillin were reported, although thrombotic complications were reported in seven infants receiving amoxicillin and two infants in the control group. There were no statistically significant differences in the incidence of necrotising enterocolitis, intracranial haemorrhage, or death.
Prophylactic vancomycin appeared to be effective in preventing catheter-related sepsis in pre-term neonates. However, the risk of bacterial resistance needs further evaluation.
Inclusion criteria for the review were clearly defined and several relevant databases were searched; search terms were reported. Publication bias was assessed and was not detected, but the authors acknowledged the potential for some publication bias. Suitable methods were used to reduce reviewer error and bias throughout the review.
Quality assessment was undertaken using a standard tool. The included vancomycin trials were of high quality, but the single amoxicillin trial had a number of methodological weaknesses, which the authors acknowledged. The trials were pooled using meta-analysis and statistical heterogeneity was explored.
Overall, given the small number of included trials and the small sample sizes, the pooled results may not be robust, so caution is warranted when interpreting the authors’ conclusions. However, the authors' recommendations for further research do appear justified.
Implications of the review for practice and research
Practice: The authors stated that insufficient evidence exists to recommend routine use of vancomycin in extremely low weight infants with central venous catheters. Prophylactic vancomycin, but not amoxicillin, is effective for preventing catheter-related blood stream infections and related morbidity in pre-term infants in neonatal intensive care units.
Research: The authors stated that more well-designed RCTs evaluating the effectiveness of prophylactic antibiotics and the potential risk for bacterial resistance are needed. A cost-effectiveness evaluation of vancomycin is also needed.
Lodha A, Furlan AD, Whyte H, Moore AM. Prophylactic antibiotics in the prevention of catheter-associated bloodstream bacterial infection in preterm neonates: a systematic review. Journal of Perinatology 2008; 28(8): 526-533
Subject indexing assigned by NLM
Antibiotic Prophylaxis; Bacteremia /prevention & control; Catheterization, Central Venous /adverse effects; Catheters, Indwelling /microbiology; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases /prevention & control; Intensive Care, Neonatal
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.