Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Mwanza, Tanzania

• Predominance of globally recognized high-risk clone ESBL-producing E. coli ST131. • First documentation and predominance of ESBL-producing K. pneumoniae ST2390 associated with bloodstream infections in the neonatology units. • The cgMLST-based Neighbor-Joining (NJ) phylogenetic analysis revealed clonal clusters involving high-risk clone ESBL-EC ST131 in medical and neonatology wards, and newly detected ESBL-KP ST2390 in neonatology ward/unit. Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) represent major clinical threats globally. Genomic epidemiological data remain scarce in low- and middle-income countries, limiting comprehensive understanding of antimicrobial-resistant pathogen diversity and clonal distribution. The present study investigated the genomic epidemiology of ESBL-EC and ESBL-KP isolates in Mwanza, Tanzania. This cross-sectional hospital-based study employed whole-genome sequencing to characterize ESBL-EC (n=39) and ESBL-KP (n=49) isolated from patients with bloodstream, urinary tract, and wound infections at a zonal referral hospital between June 2019–June 2020 and March–August 2023. Thirteen sequence types (STs) were identified among ESBL-EC, predominantly ST131 (30.7%) and ST648 (28.2%). ESBL-KP comprised 15 STs, with ST2390 (24.5%) and ST17 (18.4%) most common. The bla CTX-M-15 gene was detected in 87.2% of ESBL-EC and 95.9% of ESBL-KP. IncFII was the dominant plasmid replicon in ESBL-EC (63.9%) and ESBL-KP (83.7%), while repB was detected exclusively in ESBL-KP (28.6%), particularly among ST2390. ESBL-EC showed significantly higher resistance to ciprofloxacin (p