Emerging carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Lima, Peru

Abstract

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant public health threat, particularly in low- and middle-income countries (LMICs) with limited surveillance and treatment options. This study examines the genetic diversity, resistance patterns, and transmission dynamics of 66 CRKP isolates recovered over 5 years (2015-2019) after the first case of CRKP was identified at a tertiary care hospital in Lima, Peru. Our findings reveal a shift from bla_KPC-2 to bla_NDM-1 as the dominant carbapenemase gene after 2017. Lineage ST45 was the most prevalent and persisted for multiple years, followed by high-risk clones ST11 and ST147. The bla_NDM-1 gene was carried almost exclusively by a Tn125-like transposon, similar to the one reported in previous studies from two Peruvian hospitals. Long-read sequencing revealed nearly identical bla_NDM-carrying plasmids across the four assessed lineages. A comparative analysis of 1,023 South American CRKP genomes confirmed a unique pattern in Peru, where bla_NDM-1 (81.4%) outpaced bla_KPC-2, which remained dominant (59.4%) elsewhere. In addition, emerging clones ST45 and ST348 found in Peru were rarely found elsewhere in South America, suggesting potential regional adaptation. In conclusion, our study provides a comprehensive picture of the intra-hospital dynamics of these emerging pathogens and provides a framework for studying their genomic diversity in the understudied South American region.IMPORTANCEThis study provides novel insights into the transmission and genetic diversity of carbapenem-resistant Klebsiella pneumoniae, a bacteria responsible for severe infections, with limited treatment options. By examining isolates recovered over 5 years at a major hospital in Lima, Peru, we demonstrated a shift from one type of resistance gene, bla_KPC, to another, bla_NDM, which is more challenging to treat. Our findings reveal that specific bacterial lineages carrying the bla_NDM gene in a specific plasmid are emerging in Peru, including well-known high-risk strains and others rarely found elsewhere in South America. This pattern highlights an urgent need for targeted surveillance and infection control as these strains pose a significant challenge to healthcare systems. Our study provides crucial data on Klebsiella pneumoniae in Peru, contributing to broader efforts to monitor and control antibiotic-resistant infections in South America and globally.

Keywords: KPC-2; Klebsiella pneumoniae; NDM-1; carbapenem resistance; multidrug resistance; whole-genome sequencing.

Fig 1

Number of clinical isolates (top) and rectal isolates (bottom) of carbapenem-resistant Klebsiella pneumoniae (CRKP) recovered at the hospital’s clinical microbiology laboratory from 2015 to 2019.

Fig 2

Core-genome-based phylogeny of 66 Klebsiella spp. isolates recovered in this study. Node colors indicate the carbapenem resistance mechanism.

Fig 3

Reference-based phylogeny, resistance, and virulence genes of isolates from this study: (A) K. pneumoniae sensu stricto (n = 50), (B) K. quasipneumoniae subsp. quasipneumoniae (n = 11), and (C) K. quasipneumoniae subsp. similipneumoniae (n = 4). ST: sequence type. CRB: carbapenems. ESBL: extended-spectrum beta-lactamase. BTL: beta-lactams. AMG: aminoglycosides. SFN: sulfonamides. TMP: trimethoprim. T: tetracyclines. MC: macrolides. QNL: quinolones. C: colistin. VRL: virulence genes.

Fig 4

Reconstruction of eight NDM-carrying plasmids from four Klebsiella pneumoniae sequence types. Top: detail of the genetic context surrounding the bla_NDM-1 gene. Red: antibiotic resistance genes; Cyan: mobile genetic elements; Yellow: genes with other predicted functions. Bottom: identity-based alignment with 100%, 90%, and 70% similarity thresholds against the previously published pKpCol17ndm conjugative plasmid reported in Peru (GenBank accession number CP072906).

Fig 5

Maximum-likelihood tree of 1,071 K. pneumoniae sensu stricto sequences from South America, including CRKP sequences from this study (n = 48) and other publicly available CRKP sequences from South America (2000–2021, n = 1023).