Mutant prevention concentrations of ciprofloxacin and enrofloxacin for Salmonella enterica.
OBJECTIVE
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 10(10) 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.
Randall
L P
LP
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey, UK. l.randall@vla.defra.gsi.gov.uk
Cooles
S W
SW
Piddock
L J V
LJ
Woodward
M J
MJ
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics*; D012477:Salmonella enteritidis / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects
D000890:Anti-Infective Agents; D003510:Cyclohexanes; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D027081:DNA Gyrase