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Optimization of the use of ciprofloxacin

G Aubert1, A Carricajo, N Fonsale

  • 1Laboratoire d'Antibiologie, Hôpital Nord, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex 02, France. gerald.aubert@chu-st-etienne.fr

Pathologie-Biologie
|March 11, 2008
PubMed
Abstract

Insights

The mutant prevention concentration (MPC) of ciprofloxacin effectively inhibits resistant Escherichia coli growth. Evaluating the minimum inhibitory concentration (MIC) is crucial for determining optimal ciprofloxacin dosage in nalidixic acid-resistant strains.

Area of Science:

  • Microbiology
  • Pharmacology
  • Genetics

Background:

  • Escherichia coli (E. coli) resistance to antibiotics is a growing public health concern.
  • Understanding the genetic basis of resistance is key to developing effective treatment strategies.
  • Ciprofloxacin is a widely used antibiotic for treating E. coli infections.

Purpose of the Study:

  • To compare the mutant prevention concentration (MPC) and time-killing curves of ciprofloxacin against 11 genotyped Escherichia coli strains.
  • To investigate the correlation between specific gene mutations and ciprofloxacin resistance.
  • To determine the optimal ciprofloxacin dosage for treating E. coli infections.

Main Methods:

  • Minimum inhibitory concentrations (MICs) were determined using the E-test method.
  • Time-killing studies were conducted following NCCLS guidelines.
  • Genes gyrA, gyrB, parC, parE, and marR were amplified by PCR and sequenced to identify mutations. The MPC was defined as the lowest antibiotic concentration preventing resistant colony growth.

Main Results:

  • Strains without mutations in gyrA, gyrB, parC, parE, and marR showed low MICs (≤0.023 mg/L) and MPCs (≤0.25 mg/L).
  • Strains with two mutations (gyrA and parC) exhibited higher MICs (1.5 mg/L) and MPCs (4 mg/L).
  • Strains with a single gyrA mutation displayed a wide range of MPCs (0.5–6 mg/L) dependent on their MIC. Ciprofloxacin demonstrated bactericidal activity at 0.25 mg/L in 1 hour for susceptible strains, while resistant strains required 2–4 mg/L over 4 hours.

Conclusions:

  • Specific mutations in gyrA, gyrB, parC, and parE significantly influence ciprofloxacin resistance in E. coli.
  • The MPC is a valuable parameter for assessing the risk of resistance development.
  • For nalidixic acid-resistant E. coli strains, evaluating the MIC of ciprofloxacin is essential for optimizing treatment dosage.

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