Rowena L McMullan, Adrienne Gordon

Late-onset sepsis is associated with increased rates of mortality and morbidity in newborn infants, in addition to poorer long-term developmental outcomes and increased length of stay and hospital costs. Central line-associated blood stream infection (CLABSI) is the most common cause of late-onset sepsis in hospitalised infants, and prevention of CLABSI is a key objective in neonatal care. Increased frequency of CLABSI around the time of removal of central venous catheters (CVCs) has been reported, and use of antibiotics at the time of removal may reduce the incidence and impact of late-onset sepsis in vulnerable newborn infants. To determine the efficacy and safety of giving antibiotics at the time of removal of a central venous catheter (CVC) for reduction of morbidity and mortality in newborn infants, in particular effects on late-onset sepsis. We used the standard search strategy of the Cochrane Neonatal Review Group without language restriction to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3), MEDLINE via PubMed (1966 to 6 April 2017), Embase (1980 to 6 April 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 6 April 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised, quasi-randomised, and cluster-randomised trials considering use of any antibiotic or combination of antibiotics at the time of CVC removal in newborn infants compared with placebo, no antibiotics, or another antibiotic or combination of antibiotics. We extracted data using standard methods of the Cochrane Neonatal Review Group. Two review authors independently selected, assessed the quality of, and extracted data from the included study. Only one randomised controlled trial was eligible for inclusion in this analysis. Forty-four of a total of 88 infants received two doses of cephazolin at the time of removal of CVC compared with no antibiotics at the time of removal of CVC in the control group. No infant in the intervention group developed late-onset sepsis after CVC removal compared with five of 44 (11%) in the control group (risk ratio (RR) 0.09, 95% confidence interval (CI) 0.01 to 1.60). Cephazolin given at the time of removal of CVC did not statistically significantly alter late-onset sepsis rates and led to no significant differences in any of the prespecified outcomes. Review authors judged the study to be of low quality because of high risk of bias and imprecision. Randomised controlled trials have provided inadequate evidence for assessment of the efficacy or safety of antibiotics given at the time of CVC removal. The single identified trial was underpowered to address this question. Future research should be directed towards targeting use of antibiotics upon removal of CVC for those at greatest risk of complications from CVC removal-related CLABSI. Researchers should include safety data such as impact upon antibiotic use and resistance patterns. This investigation would best occur as part of a bundle of quality improvement care interventions provided by neonatal networks.