Plasmid-mediated quinolone resistance determinants among Gram-negative bacteraemia isolates: a hidden threat

Athanasios Margaritis1, Irene Galani2,1, Marianthi Chatzikonstantinou1

  • 14th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

Abstract

Insights

Plasmid-mediated quinolone resistance (PMQR) genes were found in 7.3% of Gram-negative bloodstream isolates. Co-existing PMQR genes significantly reduced the effectiveness of ciprofloxacin and levofloxacin.

Area of Science:

  • Medical Microbiology
  • Antimicrobial Resistance
  • Molecular Biology

Background:

  • Quinolone antibiotics are crucial for treating bacterial infections.
  • Emergence of antimicrobial resistance, particularly plasmid-mediated quinolone resistance (PMQR), poses a significant threat to public health.
  • Understanding the prevalence and impact of PMQR genes is essential for effective antimicrobial stewardship.

Purpose of the Study:

  • To determine the prevalence of eight PMQR genes in bloodstream isolates from Athens, Greece.
  • To assess the impact of PMQR genes on the in vitro activity of ciprofloxacin and levofloxacin.
  • To investigate the genetic mechanisms underlying quinolone resistance in these isolates.

Main Methods:

  • Screening of 96 Gram-negative bloodstream isolates for eight PMQR genes using PCR and sequencing.
  • Phenotypic and genotypic analysis of PMQR-positive isolates, including beta-lactamase detection, conjugation/transformation assays, time-kill assays, and mutant prevention concentration determination.
  • Detection of chromosomal mutations in gyrA and parC genes.

Main Results:

  • Seven (7.3%) isolates carried one or more PMQR genes, with qnrS1 (5.2%) and aac(6')-Ib-cr (4.2%) being the most common.
  • The presence of a single PMQR determinant generally did not confer resistance without target modification, except in Stenotrophomonas maltophilia.
  • All PMQR-positive isolates exhibited a significant inoculum effect, and co-existence of multiple PMQR genes compromised the bactericidal activity of ciprofloxacin and levofloxacin.

Conclusions:

  • PMQR genes can compromise the in vitro activity of ciprofloxacin and levofloxacin, especially when multiple genes co-exist or are expressed in a favorable genetic context.
  • PMQR determinants represent an emerging threat that can facilitate the selection of resistant mutants by widening the mutant selection window.
  • Effective strategies are needed to monitor and control the spread of PMQR genes to preserve the efficacy of quinolone antibiotics.

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