JAC Advance Access originally published online on July 8, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(3):688-691; doi:10.1093/jac/dkh360
© Crown Copyright 2004. Reproduced with the permission of the Controller of Her Majesty's Stationery Office. JAC vol.54 no.3 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Mutant prevention concentrations of ciprofloxacin and enrofloxacin for Salmonella enterica
1 Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB; 2 Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
* Corresponding author. Tel: +44-1932-357906; Fax: +44-1932-347046; Email: l.randall{at}vla.defra.gsi.gov.uk
Objectives: To determine the mutant prevention concentrations (MPCs) of ciprofloxacin and enrofloxacin against four strains of Salmonella enterica serovar Enteritidis and four strains of S. Typhimurium including one fully susceptible, one multiply resistant (MAR), one GyrA mutant and one GyrA/MAR mutant. Further, to examine mutants arising after exposure to sub-MPC concentrations of the antibiotics for susceptibility to ciprofloxacin and enrofloxacin, and cyclohexane tolerance.
Methods: MICs were determined using the agar dilution method of the BSAC. The MPC was recorded as the lowest concentration of antibiotic to inhibit growth from an inoculum of 1010 cfu.
Results: The MPCs and resulting MPC/MIC ratios of enrofloxacin were generally two- to four-fold higher than for ciprofloxacin. At 24 h for both antibiotics, MPCs were lowest for the fully susceptible strains (0.25–0.5 mg/L), similar for the MAR (1–4 mg/L) and GyrA (2–4 mg/L) mutants and highest for the GyrA/MAR mutants (1–8 mg/L). MPC/MIC ratios at 24 h were 2–16 for all strains except those for the MAR strains without mutation in gyrA where the ratios were 8–64.
Conclusions: The ability to eradicate Salmonella in vivo depends on many factors such as antibiotic susceptibility of the strain, dose and route of administration. It is suggested that these MPC values will be useful when considering dosing strategies. In view of the high MPC/MIC ratio, MAR strains with wild-type gyrA, although susceptible to ciprofloxacin (MICs 0.06–0.13 mg/L), may give rise to treatment failures.
Keywords: antibiotic resistance , cyclohexane , MAR , Typhimurium
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