Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis

Background Neonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR. Methods and findings All studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (
Sophie Wen and co-workers report a meta-analysis on bacterial isolates and antimicrobial resistance in neonatal sepsis in low- and lower-middle-income countries.
Author summary Why was this study done? Neonatal sepsis is a significant cause of childhood mortality with marked disparities across world regions and countries. Gram-negative bacteria are becoming increasingly predominant in neonatal sepsis, particularly in low- and middle-income countries, along with growing concerns of multidrug resistance. It is likely that the World Health Organization (WHO) empirical neonatal sepsis antibiotic recommendations are no longer adequate. We analysed data on neonatal sepsis from low- and lower-middle-income countries (LLMICs) to assess the burden of Gram-negative infections and associated antimicrobial resistance (AMR). What did the researchers do and find? We pooled data from 88 published studies from 19 LLMICs on neonatal sepsis (with a total of 10,458 Gram-negative isolates) and summarised the proportions of Gram-negative sepsis caused by E. coli, Klebsiella, Enterobacter, Pseudomonas, and Acinetobacter. We also examined the rates of AMR against key empirical antibiotics used in neonatal sepsis. Gram-negative bacteria accounted for 60% of neonatal sepsis in LLMICs. Regional variations in types of Gram-negative bacteria were observed, along with high rates of resistance against the WHO-recommended empirical antibiotics for neonatal sepsis. What do these findings mean? The WHO empirical antibiotic recommendations for neonatal sepsis are likely inadequate in many LLMICs. Robust AMR surveillance and reporting in LLMICs is necessary to develop region-specific empirical antibiotic recommendations for neonatal sepsis.