Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0–59 Days: A Systematic Review

Abstract

CONTEXT Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. OBJECTIVES To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. DATA SOURCES MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. STUDY SELECTION We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. DATA EXTRACTION We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. RESULTS Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization–recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41–1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.51; 95% confidence interval, 0.04–4.53; 1 trial, n = 70, very low certainty of evidence) or other outcomes. CONCLUSIONS Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.