Sequence-Based Genomic Analysis Reveals Transmission of Antibiotic Resistance and Virulence among Carbapenemase-Producing Klebsiella pneumoniae Strains.

ABSTRACT

Carbapenemase-producing Klebsiella pneumoniae (CP-Kpn) are a major concern for nosocomial infections. We previously reported an intensive care unit (ICU) outbreak of CP-Kpn. This study investigated the transmission pattern and genetic characteristic of CP-Kpn in the hospital during the outbreak period. Whole-genome sequencing was retrospectively performed on 173 CP-Kpn isolates. Pairwise single-nucleotide polymorphism (SNP) distances were calculated to determine SNP thresholds for clustering. Plasmids and mobile genome elements (MGEs) were identified through short- and long-read sequencing. Strains were classified into three groups, sequence type 11 (ST11) (86.12%), ST15 (9.83%), and other ST. An SNP threshold of 16 revealed a 66.47% clustering rate. ICU admission and meropenem use proportions were significantly higher in clustered patients than in unique patients. MGE distribution was consistent with the phylogenetic tree. Of the isolates, 53.18% were CP-Kpn with hypervirulence genes. We identified five plasmids carrying virulence genes, and four of them have not been previously reported. Clonal transmission was the main cause of CP-Kpn infections in the hospital. Multidrug resistance genes and MGE variations were correlated with clustering. Finally, four novel plasmids carrying virulence genes were identified. The findings highlight the control of CR-Kpn transmission through prevention measures to reduce nosocomial infections. IMPORTANCE In this study, we combined genomic and epidemiological analyses and defined an optimal cutoff value for SNP difference that could be used to aid investigation in tertiary hospital in China. We revealed clonal transmission was the main cause of CP-Kpn infections in the hospital and identified four novel plasmids carrying virulence genes. Our results strongly suggested that dominant CP K. pneumoniae strains lead to outbreaks and described different evolutionary patterns of plasmids carrying multidrug resistance and virulence genes.