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

Habib Bourguiba Hospital in Sfax, Tunisia, a 500-bed regional medical center, experienced profound increases in carbapenemase-producing Klebsiella pneumoniae (CPK) infections over 2009-2022. To implement improved control measures, we leveraged clinical microbiologic results on 1013 unique CPK, followed by targeted genomic analyses to conduct high-resolution clustering of strains and evaluate replicons mobilizing carbapenemases and other forms of resistance. Analyses resolved transmission chains, reservoirs, and informed approaches to facilitate improved infection control and prevention. Hospital-acquired CPK increased >10-fold over 2009-2022, from 0{middle dot}95 to 9{middle dot}59 cases per 10000 patient days. OXA-48-like enzymes occurred most frequently (730 strains, 56{middle dot}7%), followed by NDMs (281, 43{middle dot}1%), or both (207, 26{middle dot}9%). Genomic analyses revealed 23 genomic sequence types (STs), with dynamic shifts among clusters within ST101, ST147, and ST383 (70% of isolates). In 2009, ST383 carrying blaOXA-204 in IncC arose first, followed by ST101 carrying blaOXA-48 on IncL/M in 2011, and ST147 carrying blaNDM-1 on IncFIB (pQIL)/IncFII multi-replicon plasmids in 2014. Since 2019, emerging epidemic strains of ST383 carrying blaNDM-5 and blaOXA-48 on hybrid IncFIB/IncHI1B virulence plasmids became dominant, highlighting the capacity of these lineages to disseminate and sustain nosocomial outbreaks. Clustering with 80,252 K. pneumoniae genomes within the internationally available FDA GenomeTrakr and NCBI Pathogen Detection tools placed Tunisian strains within the broader global context, of which 82% STs clustered with Mediterranean and global clusters, while 18% remained unique to the hospital. Findings identified local through international reservoirs of strain entry into the hospital and supported clinical microbiologic approaches for patient surveillance and rapid assessments to identify putative outbreaks.