Optimization of the use of ciprofloxacin.
OBJECTIVE
To compare mutant prevention concentration (MPC) of ciprofloxacin and time-killing curve with regards to 11 genotyped Escherichia coli.


METHODS
MICs were determined using the E-test method. Time-killing studies were performed in accordance with the NCCLS guidelines. The genes gyrA, gyrB, parC, parE and marR were amplified by PCR and sequenced. The MPC was defined as the lowest antibiotic concentration preventing the growth of resistant colonies when 10(10) CFU/mL were spread on a solid medium.


RESULTS
Strains with no genes gyrA, gyrB, parC, parE and marR mutation presented MIC less or equal to 0.023 mg/L and MPC less or equal to 0.25 mg/L. Strains with two mutations (gyrA and parC) presented MIC equal to 1.5 mg/L and MPC equal to 4 mg/L. Strains with one mutation (gyrA) presented MIC less or equal to 0.75 mg/L, but MPC ranged from 0.5 to 6 mg/L depending of the MIC of ciprofloxacin. The time-killing curves for ciprofloxacin showed a bactericidal activity of 0.25 mg/L in 1h for strains without mutation, compared with a bactericidal activity of 2 and 4 mg/L in 4h for strains with one and two mutations, respectively.


CONCLUSIONS
For strains of E. coli resistant to nalidixic acid, it was necessary to evaluate the MIC of ciprofloxacin in order to asses the optimal dosage of ciprofloxacin.
Aubert
G
G
Laboratoire d'Antibiologie, Hôpital Nord, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex 02, France. gerald.aubert@chu-st-etienne.fr
Carricajo
A
A
Fonsale
N
N
Vautrin
A-C
AC
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005784:Gene Amplification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology; D016133:Polymerase Chain Reaction
D000890:Anti-Infective Agents; D009268:Nalidixic Acid; D002939:Ciprofloxacin