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Pathogen sequencing has been used to investigate case clusters and confirm nosocomial transmission in a small number of neonatal units. Here we utilise pathogen sequence data to estimate the fraction of\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      neonatal sepsis attributable to nosocomial transmission in African and South Asian countries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We estimated the proportion of invasive\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      disease involved in nosocomial transmission clusters in a given neonatal unit, using single-linkage clustering based on pairwise temporal and genetic distances estimated from bacterial whole-genome sequences aggregated from 10 contributing studies. Analysing 1,523\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      isolates from 27 units in 13 countries in Africa and South Asia between 2013 and 2023, we inferred 156 nosocomial transmission clusters, ranging from 2 to 188 neonates each (83 of the clusters comprised \u22653 cases). Overall, we estimated that 1,035 neonatal infections (68.0%) were part of nosocomial transmission clusters. Excluding the first infection in each cluster as a potential index case, we estimate at least 879 (57.7%) infections were acquired via nosocomial transmission. Sensitivity analyses showed that results were robust to the choice of genetic distance estimation methods and thresholds used to define clusters, and cluster estimates were stable over temporal distance thresholds ranging from 2 to 8 weeks. Isolates were mostly extended-spectrum beta-lactamase (ESBL) producers (90.9%) and included 172 multi-locus sequence types (STs). Fourteen STs, including several globally recognised multidrug-resistant lineages, were associated with transmission clusters at multiple units, and these were collectively responsible for two-thirds of all infections. Carriage of carbapenemase genes (adjusted odds ratio, aOR = 2.08 [95% confidence interval, CI: 1.04, 4.14];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and ESBL genes (aOR = 2.48 [95% CI: 1.26, 4.90];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006) were significantly positively associated with transmission in a logistic regression model with site as a covariate. Limitations of this study include the lack of sufficient clinical data to allow high-resolution investigation of transmission dynamics and lack of facility-level data to investigate contributors to the observed differences in transmission burden across sites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Nosocomial transmission contributes to a substantial proportion of\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      sepsis in neonatal care units in Africa and South Asia. Reducing transmission within these settings through improved infection prevention and control and other measures could substantially reduce the neonatal sepsis burden. A high burden of transmission clusters is associated with the same drug-resistant lineages that are recognised as high-risk clones associated with hospital outbreaks in high-income countries, indicating global connectivity of the antimicrobial-resistant pathogen population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1005077","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:52:07Z","timestamp":1778694727000},"page":"e1005077","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Contribution of nosocomial transmission to Klebsiella pneumoniae neonatal sepsis in Africa and South Asia: An observational study of infection clusters inferred from pathogen genomics and temporal data"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-9403","authenticated-orcid":true,"given":"Erkison 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Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/newborn-mortality"},{"issue":"8","key":"pmed.1005077.ref002","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/archdischild-2020-320217","article-title":"Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis","volume":"106","author":"C Fleischmann","year":"2021","journal-title":"Arch Dis Child"},{"key":"pmed.1005077.ref003","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study","volume":"395","author":"KE Rudd","year":"2020","journal-title":"Lancet"},{"issue":"11","key":"pmed.1005077.ref004","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/S1473-3099(19)30414-1","article-title":"Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan 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