Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

Diagn Microbiol Infect Dis. 2019 Mar;93(3):250-257. doi: 10.1016/j.diagmicrobio.2018.10.004. Epub 2018 Oct 13.

Abstract

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) blaKPC, 20.8% (5/24) blaNDM, 20.8% (5/24) blaSME, 8.3% (2/24) blaIMP, and 4.2% (1/24) blaVIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing blaKPC were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and metallo β-lactamase-positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were identical by whole genome sequencing. At this health system, CRE were mediated by diverse mechanisms with predictable susceptibility to newer β-lactamase inhibitors.

Keywords: Avibactam; Carbapenem-resistant Enterobacteriaceae; Carbapenemase; Porin; Relebactam; Vaborbactam.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • California / epidemiology
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / genetics*
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Carbapenem-Resistant Enterobacteriaceae / metabolism
  • Child
  • Child, Preschool
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology*
  • Female
  • Gene Expression
  • Genetic Variation
  • Genome, Bacterial / genetics
  • Genotype
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Epidemiology
  • Phenotype
  • Porins / deficiency
  • Porins / genetics
  • Young Adult
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / deficiency
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Porins
  • beta-Lactamase Inhibitors
  • beta-Lactamases
  • carbapenemase