Contribution of nosocomial transmission to Klebsiella pneumoniae neonatal sepsis in Africa and South Asia: a meta-analysis of infection clusters inferred from pathogen genomics and temporal data
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Background
Klebsiella pneumoniae is the leading cause of sepsis among neonates in low- and middle-income countries (LMICs) in Africa and Asia, contributing substantially to the overall burden of antimicrobial resistant (AMR) infections and mortality among neonates globally. 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 K. pneumoniae neonatal sepsis attributable to nosocomial transmission in African and South Asian countries.
Methods and Findings
We estimated the proportion of invasive K. pneumoniae 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. Analysing 1,523 K. pneumoniae isolated 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 ≥3 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 were associated with transmission clusters at multiple units and these were collectively responsible for two-thirds of all infections. Clustered isolates compared with singletons were more likely to carry carbapenemase genes (19.9% vs 10.2%, P = 0.003) or ESBL genes (94.2% vs 81.8%, P < 0.001).
Conclusions
Nosocomial transmission contributes to a substantial proportion of K. pneumoniae 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.
