Mutant prevention concentration for ciprofloxacin and levofloxacin with Pseudomonas aeruginosa

Glen T Hansen1, Xilin Zhao, Karl Drlica

  • 1Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Insights

Ciprofloxacin and levofloxacin mutant prevention concentrations (MPC) were determined for Pseudomonas aeruginosa. Ciprofloxacin demonstrated higher activity against resistant mutant subpopulations compared to levofloxacin.

Area of Science:

  • Microbiology
  • Pharmacology
  • Antimicrobial Resistance

Background:

  • Fluoroquinolones are critical antibiotics for treating Pseudomonas aeruginosa infections.
  • Understanding the mutant prevention concentration (MPC) is crucial for optimizing antibiotic therapy and preventing resistance.
  • Pseudomonas aeruginosa is an opportunistic pathogen known for developing antimicrobial resistance.

Purpose of the Study:

  • To determine the mutant prevention concentration (MPC) of ciprofloxacin and levofloxacin against Pseudomonas aeruginosa.
  • To compare the activity of ciprofloxacin and levofloxacin against resistant mutant subpopulations.
  • To assess the correlation between MPC and minimum inhibitory concentration (MIC) for these fluoroquinolones.

Main Methods:

  • Population analysis was used to determine MPCs for fluoroquinolone-susceptible Pseudomonas aeruginosa isolates.
  • Agar-based methods were employed to identify resistant mutants at high drug concentrations.
  • A modified MPC estimation method was used to survey 151 clinical isolates.

Main Results:

  • The MPCs for ciprofloxacin and levofloxacin in susceptible isolates were 3 mg/L and 9.5 mg/L, respectively.
  • Modal MPCs for clinical isolates were 2 mg/L for ciprofloxacin and 8 mg/L for levofloxacin.
  • Ciprofloxacin showed 3-4 times greater activity than levofloxacin against resistant mutant subpopulations; MPC correlated poorly with MIC.

Conclusions:

  • Ciprofloxacin is more effective than levofloxacin in preventing the emergence of resistance in Pseudomonas aeruginosa.
  • The MPC is a valuable parameter for assessing the potential of fluoroquinolones to prevent resistance.
  • Further research is needed to understand the clinical implications of MPC and MIC correlations.