Genomic characterization of Klebsiella pneumoniae causing invasive disease in South African infants: observational studies between 2018 to 2023

Abstract Background Klebsiella pneumoniae (KPn) is a leading cause of invasive bacterial disease in African children, albeit with a scarcity of genotypic characterization. Methods We sequenced invasive KPn isolates from infants ≤90 days, collected through observational hospital surveillance (n = 226) between March 4th, 2019 to February 27th, 2021, and between May 13th, 2022 to October 31st, 2023, and postmortem sampling (n = 111) between February 15th, 2018 to April 18th, 2023. Postmortem Kpn isolates were attributed in the causal pathway to death by the determination of the cause of death (DeCoDe) panel, which consists of local experts. Results Three hundred and thirty-seven isolates (226 identified during hospital surveillance and 111 from postmortem sampling) were included in the final analysis. Genomic analysis identified 85 distinct clonotypes. Sequence type (ST)17 (22.0%) predominated, followed by ST39 (12.7%). The dominant K-locus (KL) were KL25 (24.0%), KL2 (14.5%), and KL149 (13/4%), while the dominant O-antigens included O1αβ,2α(48.4%), and O5 (19.9%). Eighty-five percent (287/337) of the KPn isolates harboured multi-drug resistant (MDR) genes, including 32.9% to carbapenems. Notably, blaOXA-181, blaNDM-5, and blaNDM-1 were detected in 26.4%, 2.1% (7/337), and 0.3% (1/337) of isolates, respectively. Conclusion Although a wide diversity of strains were associated with Kpn invasive disease, over 80% of the cases were attributed to eleven K loci. These data provide critical insights into KPn epidemiology and highlight potential antigen targets for vaccine development in young African children.