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The mutant selection window and antimicrobial resistance

Karl Drlica1

  • 1Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA. drlica@phri.org

The Journal of Antimicrobial Chemotherapy
|June 14, 2003
PubMed

Insights

The mutant selection window (MSW) defines a critical antimicrobial concentration range. Concentrations within the MSW can promote resistant bacteria, while those above it inhibit their growth, guiding effective antimicrobial therapy.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • The mutant selection window (MSW) is the antimicrobial concentration range between the minimal concentration for wild-type bacterial growth inhibition and the mutant prevention concentration (MPC).
  • Antimicrobial concentrations within the MSW are known to selectively enrich resistant bacterial mutants.
  • Understanding the MSW is crucial for developing strategies to combat antimicrobial resistance.

Purpose of the Study:

  • To define the mutant selection window (MSW) and its implications for antimicrobial resistance.
  • To explore the relationship between MSW, antimicrobial pharmacokinetics, and bacterial populations.
  • To identify strategies for preventing the enrichment of resistant mutants.

Main Methods:

  • Defining the mutant selection window (MSW) based on bacterial susceptibility data.
  • Analyzing the relationship between MSW dimensions and antimicrobial pharmacokinetics.
  • Evaluating the impact of antimicrobial concentrations relative to the MSW on bacterial populations.

Main Results:

  • The MSW is a characteristic range for each pathogen-antimicrobial combination.
  • Antimicrobial concentrations within the MSW promote the selection and enrichment of resistant mutants.
  • Antimicrobial concentrations above the MSW restrict the enrichment of resistant mutants.

Conclusions:

  • The MSW is a key concept for understanding and predicting antimicrobial resistance development.
  • Linking MSW characteristics with pharmacokinetics can help rank antimicrobial compounds and dosing regimens.
  • Combination therapy is recommended when antimicrobial concentrations cannot be maintained above the MSW to prevent mutant enrichment.

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