{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:40:52Z","timestamp":1791412852765,"version":"4.3.3"},"reference-count":123,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011334","name":"Health Innovation, Investment and Research Office","doi-asserted-by":"publisher","award":["Advancing Clinical Research Fellowship"],"award-info":[{"award-number":["Advancing Clinical Research Fellowship"]}],"id":[{"id":"10.13039\/100011334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1197743"],"award-info":[{"award-number":["APP1197743"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1193826"],"award-info":[{"award-number":["APP1193826"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1177777"],"award-info":[{"award-number":["APP1177777"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1173857"],"award-info":[{"award-number":["APP1173857"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      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 (&lt;10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      ,\n                      <jats:italic>Enterobacter<\/jats:italic>\n                      ,\n                      <jats:italic>Pseudomonas<\/jats:italic>\n                      ,\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      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%).\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      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\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      spp. in Asia and\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1003787","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T14:26:08Z","timestamp":1632839168000},"page":"e1003787","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":142,"title":["Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-4443","authenticated-orcid":true,"given":"Sophie C. 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L.","family":"Paterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-6789","authenticated-orcid":true,"given":"Adam D.","family":"Irwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"issue":"9938","key":"pmed.1003787.ref001","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0140-6736(14)60496-7","article-title":"Every Newborn: progress, priorities, and potential beyond survival","volume":"384","author":"JE Lawn","year":"2014","journal-title":"Lancet"},{"key":"pmed.1003787.ref002","volume-title":"Reaching the Every Newborn national 2020 milestones: country progress, plans and moving forward.","author":"World Health 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