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Related Experiment Videos

Resistance to quinolones.

R P Mouton1

  • 1Department of Medical Microbiology, University Hospital, Leiden, The Netherlands.

Pharmaceutisch Weekblad. Scientific Edition
|December 11, 1987
PubMed
Summary
This summary is machine-generated.

Bacterial resistance to quinolones arises from specific mutations. While in vitro studies show low resistance rates, clinical fluoroquinolone resistance remains rare, except in Pseudomonas aeruginosa and staphylococci.

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Quinolone resistance in bacteria is primarily driven by chromosomal mutations.
  • The specific mutation locus dictates the mechanism and spectrum of quinolone resistance.
  • Fluoroquinolone resistance mechanisms involve alterations in bacterial enzymes like gyrase.

Purpose of the Study:

  • To investigate the mutation rates and mechanisms of bacterial resistance to quinolones.
  • To evaluate the development of combined resistance to quinolones and other antibiotics.
  • To assess the clinical relevance of fluoroquinolone resistance.

Main Methods:

  • In vitro studies using high inocula to determine mutation rates.
  • Serial transfer of bacterial strains in increasing quinolone concentrations.

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  • Analysis of outer membrane protein changes in resistant mutants.

    • Main Results:

    • Low mutation rates (10^-6 to 10^-12) for fluoroquinolone resistance were observed in vitro.
    • In vitro exposure led to increased Minimum Inhibitory Concentrations (MICs) for most quinolones.
    • MICs for potent fluoroquinolones like ciprofloxacin often remained below achievable in vivo concentrations, except for Pseudomonas aeruginosa and staphylococci.
    • Combined resistance to quinolones and other antibiotics was observed in vitro and in high-inoculum mutants.
    • Alterations in outer membrane proteins were identified in resistant mutants.

    Conclusions:

    • Bacterial quinolone resistance is mutation-dependent, with locus-specific mechanisms.
    • In vitro resistance development does not always correlate with clinical outcomes.
    • Clinical fluoroquinolone resistance is infrequent, with notable exceptions in Pseudomonas aeruginosa and staphylococci.