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Mechanisms responsible for cross-resistance and dichotomous resistance among the quinolones

C C Sanders1

  • 1Center for Research in Anti-Infectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. ecsanders@earthlink.net

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|March 16, 2001
PubMed

Insights

Quinolone resistance develops through stepwise mutations affecting drug targets, permeability, or efflux. Understanding this process allows prediction of effective therapies using an 8-fold rule to minimize resistance selection.

Area of Science:

  • Microbiology
  • Pharmacology
  • Genetics

Background:

  • Quinolone antibiotics are crucial for treating bacterial infections.
  • Resistance to quinolones is a growing public health concern.
  • Mechanisms of resistance involve mutations in chromosomal genes.

Purpose of the Study:

  • To elucidate the stepwise process of quinolone resistance development.
  • To identify patterns of cross-resistance and dichotomous resistance.
  • To develop a predictive rule for selecting effective quinolones and minimizing resistance.

Main Methods:

  • Analysis of mutation accumulation in bacterial chromosomal genes.
  • Quantification of susceptibility changes (4- to 8-fold) per mutation step.
  • Examination of cross-resistance patterns with different quinolones.
  • Evaluation of organism- and quinolone-specific resistance pathways.

Main Results:

  • Quinolone resistance evolves via a stepwise accumulation of mutations.
  • Each mutation typically reduces susceptibility by 4- to 8-fold.
  • Resistance pathways vary significantly based on the quinolone and organism.
  • Observed patterns include cross-resistance and dichotomous resistance.

Conclusions:

  • Understanding the stepwise evolution of quinolone resistance is key.
  • An '8-fold rule' can predict effective therapies and minimize resistance.
  • This knowledge aids in optimizing antibiotic treatment strategies.

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