Escalating burden and mortality of carbapenem-resistant Klebsiella pneumoniae species complex infections in Bangladeshi infants.

Klebsiella pneumoniae infections in young infants are an escalating threat in low- and middle-income countries, yet robust longitudinal data integrating hospital burden, clinical outcomes, antimicrobial resistance, and genomics remains scarce. We performed an 18-year (2004-2021) prospective, multicenter genomic epidemiology study across four hospitals in Bangladesh. Among 122,353 enrolled children from whom blood and/or cerebrospinal fluid cultures were performed, 1600 (1.3%) yielded culture-confirmed Klebsiella pneumoniae species complex (KpSC) isolates. Positivity increased from 16 per 1000 cases tested in 2004 to 37 per 1000 in 2021. Hospital case-fatality rate (CFR) rose from 21.4% to 51.4% during the study, paralleling the emergence and expansion of carbapenem resistance, first detected in 2008 and reaching 81% of isolates by 2021. Neonates accounted for 80.5% of infections and experienced a CFR of 40.8%. Whole-genome sequencing of 599 representative isolates revealed four KpSC species, 145 sequence types, and 92 capsular alleles. Global high-risk clones ST11, ST16, and ST147 harbouring NDM-type carbapenemases dominated recent cases. These findings document the increasing resistance and mortality associated with KpSC infections amongst neonates in Bangladesh, underscoring the urgent need for strengthened infection prevention and control, equitable access to effective combination therapies, and vaccine-based preventative strategies.