Prospective Genomic Surveillance of Severe Febrile Illness in Tanzanian Children Identifies High Mortality and Resistance to First-Line Antibiotics in Bloodstream Infections.

We evaluated the prevalence, pathogen profile, and antimicrobial resistance (AMR) patterns of bloodstream infections (BSIs) among 392 children with severe febrile illness who presented (July 26, 2022-September 20, 2023) to a referral hospital in Tanzania. We identified a causative pathogen in 9.8% (n=38) of participants. Blood culture analysis confirmed BSI in 5.2% (n=20) of participants with a case fatality rate of 45%. Whole genome sequencing (WGS) of blood culture isolates identified gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae) as the predominant pathogens, many exhibiting extended-spectrum beta-lactamase (ESBL) resistance genes (CTX-M-15, CTX-M-27), rendering them resistant to first-line antimicrobials. We also observed probable nosocomial transmission in ventilated patients based on phylogenetic analyses of tracheal aspirate isolates. There is an urgent need for enhanced AMR surveillance, empiric antibiotic regimens tailored to local AMR patterns, culture-independent diagnostics, and robust infection control practices in resource-limited settings to mitigate BSI-related mortality and minimize nosocomial transmission risk.