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Mutant selection window hypothesis updated.

Karl Drlica1, Xilin Zhao

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

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
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Summary
This summary is machine-generated.

Optimizing antimicrobial dosing requires understanding the mutant selection window. This concentration range can lead to drug-resistant mutants, necessitating strategies like the mutant prevention concentration to improve treatment outcomes.

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Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • The mutant selection window (MSW) hypothesis explains how antimicrobial concentrations can select for drug-resistant mutants.
  • Understanding this window is crucial for effective antimicrobial therapy and preventing resistance.

Purpose of the Study:

  • To explore the relationship between the mutant prevention concentration (MPC) and antimicrobial dosing strategies.
  • To provide a framework for optimizing antimicrobial regimens to prevent the emergence of resistance.

Main Methods:

  • Correlating the static MPC (measured via agar plates) with dynamic drug concentrations in vitro and in vivo.
  • Analyzing the impact of stepwise acquisition of resistance on the MSW.
  • Evaluating the utility of the area under the concentration-time curve (AUC) divided by MPC as a dosing index.

Main Results:

  • The MSW hypothesis provides a basis for antimutant dosing strategies.
  • Stepwise resistance acquisition widens the MSW, complicating mutant suppression.
  • A clinical case highlights concurrent resistance development and susceptible cell eradication.

Conclusions:

  • The mutant selection window is a valuable concept for optimizing antimicrobial dosing.
  • Antimutant dosing regimens, guided by the MPC, can improve treatment efficacy.
  • Further research into MSW-guided dosing is warranted to combat antimicrobial resistance.