Leveraging the global genomic epidemiology of carbapenemase-producing <i>Klebsiella pneumoniae</i> to inform infection prevention in Tunisian hospitals

Abstract

ABSTRACT Carbapenemase-producing Klebsiella pneumoniae (CPK) is a major threat in North Africa, yet long-term genomic surveillance efforts remain scarce. To address this, we analyzed 1,013 CPK clinical isolates collected at Habib Bourguiba Hospital (Sfax, Tunisia) from 2009 to 2022. Given limited genomic resources, clinical microbiologic and pulse-field gel electrophoresis (PFGE) profiles identified representative isolates for genomic analyses to resolve transmission dynamics and plasmid dissemination over time. Hospital-acquired CPK increased &gt;10-fold, from 0.95 to 9.59 per 10,000 patient-days. OXA-48-like enzymes predominated, followed by NDMs and dual producers. Genomic analyses identified 23 sequence types, with ST101, ST147, and ST383 accounting for 70% of isolates. ST383 strains carrying bla OXA-204 on IncC plasmids occurred first, followed by ST101 with bla OXA-48 on IncL replicons and ST147 with bla NDM-1 on IncFIB/IncFII multi-replicons. Since 2019, epidemic ST383 co-harboring bla OXA-48 on IncL plasmids and bla NDM-5 with rmpA/iuc on hybrid IncFIB/IncHI1B plasmids became dominant. Comparison with 80,252 global genomes in NCBI Pathogen Detection showed that 82% of study isolates clustered with Mediterranean/global lineages, demonstrating frequent international dissemination. Findings reveal both local and international reservoirs driving CPK introductions, informing targeted infection-control strategies in regional hospitals.