Clinical outcomes and plasmid-associated features in KPC-producing Klebsiella pneumoniae bacteraemia

The genetic epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) is geographically distinct. This study aimed to investigate the association of capsular types and plasmid-mediated factors with mortality in patients with CRKP bacteraemia.

Patients with CRKP bacteraemia were enrolled at two medical centres between 2017 and 2021. Capsular typing, antimicrobial susceptibility testing, polymerase chain reaction (PCR) for carbapenemase-encoding genes in all strains, and whole-genome sequencing (WGS) of selected strains were performed.

Among 402 patients with monomicrobial CRKP bacteraemia, 238 (59.2%) strains were carbapenemase-producing. Of the K47 strains (n = 188), 89.9% carried bla_KPC; of the K64 (n = 44) strains, 43.2% carried bla_KPC or bla_OXA-48-like. In a multivariate Cox analysis, bla_KPC was a significant predictor of mortality specifically in K64 (aHR = 3.64; p = 0.004) but not in K47. Other carbapenemase genes did not show significant association with their capsular types. WGS identified the 85 selected isolates as ST11 or ST11-1LV; among them, K64-bla_KPC(+) strains (n = 11) clustered separately from K64-bla_KPC(-) (n = 33) and K47-bla_KPC(+) strains (n = 41). Plasmid structure analysis revealed the distinctness of K64-associated bla_KPC plasmids which were generally larger than those in K47 and characterized by the presence of a 57-kb region encoding a T4SS module along with Escherichia coli virulence genes traT and traJ. Among 188 KPC-producing K. pneumoniae, independent mortality predictors included Pitt score (aHR = 1.27; p < 0.001), pneumonia (aHR = 1.84; p = 0.01), and ceftazidime-avibactam treatment (aHR = 0.38, p = 0.002). Capsular type was significantly prognostic (p = 0.02), with K47 showing a reduced risk of death (aHR = 0.33; p = 0.009) compared to other types. Additionally, traT was identified as a potential marker for fatal outcomes (aHR = 3.12; p = 0.05).

Capsular types and the structural characteristics of bla_KPC plasmids are associated with clinical outcomes in CRKP bacteraemia. Although traT is a putative marker for high-risk lineages, clinical severity remains the primary predictor of mortality. The capsular type-specific distribution of conjugative plasmids and the co-carriage of traT with bla_KPC suggest a potential route for the concurrent dissemination of resistance and lineage-associated genetic features.