Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain

Enferm Infecc Microbiol Clin. 2017 Oct;35(8):487-492. doi: 10.1016/j.eimc.2016.05.006. Epub 2016 Jun 23.
[Article in English, Spanish]

Abstract

Background: Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC β-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates.

Methods: The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC β-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals.

Results: Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates.

Conclusion: qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC β-lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints.

Keywords: Acquired AmpC β-lactamases; Betalactamasas de clase C adquiridas; Carbapenemasas; Carbapenemases; Mecanismos de resistencia a quinolonas; Quinolone resistance mechanisms.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology*
  • Fluoroquinolones / pharmacology*
  • Genes, Bacterial
  • Humans
  • Nalidixic Acid / pharmacology
  • R Factors / genetics
  • Spain / epidemiology
  • beta-Lactam Resistance / genetics
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Bacterial Proteins
  • Fluoroquinolones
  • Nalidixic Acid
  • AmpC beta-lactamases
  • beta-Lactamases
  • carbapenemase