Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients

Nat Commun. 2023 Dec 21;14(1):8495. doi: 10.1038/s41467-023-44285-w.

Abstract

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Escherichia coli / genetics
  • Escherichia coli Infections* / microbiology
  • Genetic Variation
  • Humans
  • Klebsiella
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • Retrospective Studies
  • beta-Lactamases / genetics

Substances

  • beta-Lactamases
  • Anti-Bacterial Agents