Randomized controlled trials of antibiotics for neonatal infections: a systematic review

Antibiotics are a key resource for the management of infectious diseases in neonatology and their evaluation is particularly challenging. We reviewed medical literature to assess the characteristics and quality of randomized controlled trials on antibiotics in neonatal infections.

We performed a systematic search of PubMed, Embase and the Cochrane Library from January 1995 to March 2010. Bibliographies of relevant articles were also hand-searched. We included all randomized controlled trials that involved neonates and evaluated the use of an antibiotic agent in the context of a neonatal infectious disease. Methodological quality was evaluated using the Jadad scale and the Cochrane Risk of Bias Tool. Two reviewers independently assessed studies for inclusion and evaluated methodological quality.

A total of 35 randomized controlled trials were evaluated. The majority were conducted in a single hospital institution, without funding. Median sample size was 63 (34-103) participants. The most frequently evaluated antibiotic was gentamicin. Respectively, 18 (51%) and 17 (49%) trials evaluated the therapeutic or prophylactic use of antibiotics in various neonatal infections. Overall, the methodological quality was poor and did not improve over the years. Risk of bias was high in 66% of the trials.

Design and reporting of randomized controlled trials of antibacterial agents in neonates should be improved. Nevertheless, the necessity of implementing such trials when antibacterial efficacy has already been established in other age groups may be questioned and different methods of evaluation should be further developed.