{"id":"doi:10.1371/journal.pmed.1003787","kind":"review","title":"Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis","authors":["Sophie Chien-Hui Wen","Yukiko Ezure","Lauren Rolley","Geoffrey Spurling","Colleen L. Lau","Saba Riaz","David Leslie Paterson","Adam Irwin"],"author_count":8,"year":2021,"published":"2021-09-28","venue":"PLoS Medicine","cited_by":161,"doi":"10.1371/journal.pmed.1003787","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1371/journal.pmed.1003787","archive_url":"https://space-kitty.com/papers/doi:10.1371/journal.pmed.1003787","updated":null,"pmid":"34582466","pmcid":null,"openalex_id":"W3203515993","pdf_url":"https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003787&type=printable","abstract":"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 (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria. CONCLUSIONS: Gram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Neonatal and Maternal Infections"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis\" by Sophie Chien-Hui Wen, Yukiko Ezure, Lauren Rolley et al., https://doi.org/10.1371/journal.pmed.1003787, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"infectious-disease-amr","name":"Infectious Disease, Vaccines & Antimicrobial Resistance","domain_slug":"medicine"}],"cited_in_dossiers":[]}