Genomic epidemiology of Klebsiella pneumoniae in Italy and novel insights into the origin and global evolution of its resistance to carbapenem antibiotics

Antimicrob Agents Chemother. 2015 Jan;59(1):389-96. doi: 10.1128/AAC.04224-14. Epub 2014 Nov 3.

Abstract

Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ∼ 1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Typing Techniques
  • Base Sequence
  • Carbapenems / therapeutic use*
  • Cross Infection / microbiology
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Evolution, Molecular
  • Humans
  • Italy / epidemiology
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • DNA, Bacterial
  • beta-Lactamases