Expanding threat of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Peru: genomic and phenotypic evidence of high-risk clones dissemination

Carbapenemase-producing Enterobacterales represent a growing global threat due to their extensive antimicrobial resistance and rapid dissemination. This study characterized the phenotypic and genomic features of Escherichia coli and Klebsiella pneumoniae isolates collected between 2020 and 2022 from four healthcare institutions in Lima, Peru. A total of 320 non-redundant isolates (61 E. coli and 259 K. pneumoniae ) were analyzed through antimicrobial susceptibility testing, polymerase chain reaction, and whole-genome sequencing. The most frequent carbapenemase gene was bla NDM (69%), followed by bla KPC (16.9%) and bla OXA-48-like (4.6%). Eleven K. pneumoniae isolates co-produced NDM and KPC, and one E. coli isolate co-harbored NDM and OXA-48-like. All isolates were multidrug-resistant, and 5% were resistant to all agents included in the routine panel; however, aztreonam/avibactam and cefiderocol retained complete in vitro activity among tested isolates. Novel β-lactam/β-lactamase inhibitor combinations such as aztreonam/avibactam and cefiderocol showed complete activity against all classes of carbapenemases. Genomic analysis revealed predominant E. coli sequence types ST167 and ST410 and K. pneumoniae lineages ST147, ST15, ST45, and ST273. The bla NDM-5 allele was detected for the first time in Peru, mostly in E. coli ST167 , and was carried on multireplicon IncF-type plasmids. In K. pneumoniae , ST147 was identified as a dominant clone associated with bla NDM-1 , indicating sustained local dissemination of high-risk clonal groups. The coexistence of multiple carbapenemases and plasmid backbones highlights the ongoing evolution of resistance mechanisms. This work provides the first integrative genomic overview of carbapenemase-producing E. coli and K. pneumoniae in Peru and underscores the need for continuous genomic surveillance and antimicrobial stewardship to mitigate their clinical and epidemiological impact.