Escalating carbapenem-resistant Klebsiella burden and mortality 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, 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 or cerebrospinal fluid cultures were performed, 1,600 (1.3%) yielded culture-confirmed Klebsiella pneumoniae species complex (KpSC) isolates. Positivity increased from 16 per 1,000 cases tested in 2004 to 37 per 1,000 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 & control, equitable access to effective combination therapies, and vaccine-based preventative strategies.