title: Modification of enrofloxacin treatment regimens for poultry experimentally infected with Salmonella enterica serovar Typhimurium DT104 to minimize selection of resistance.
abstract: We hypothesized that higher doses of fluoroquinolones for a shorter duration could maintain efficacy (as measured by reduction in bacterial count) while reducing selection in chickens of bacteria with reduced susceptibility. Chicks were infected with Salmonella enterica serovar Typhimurium DT104 and treated 1 week later with enrofloxacin at the recommended dose for 5 days (water dose adjusted to give 10 mg/kg of body weight of birds or equivalence, i.e., water at 50 ppm) or at 2.5 or 5 times the recommended dose for 2 days or 1 day, respectively. The dose was delivered continuously (ppm) or pulsed in the water (mg/kg) or by gavage (mg/kg). In vitro in sera, increasing concentrations of 0.5 to 8 microg/ml enrofloxacin correlated with increased activity. In vivo, the efficacy of the 1-day treatment was significantly less than that of the 2- and 5-day treatments. The 2-day treatments showed efficacy similar to that of the 5-day treatment in all but one repeat treatment group and significantly (P < 0.01) reduced the Salmonella counts. Dosing at 2.5x the recommended dose and pulsed dosing both increased the peak antibiotic concentrations in cecal contents, liver, lung, and sera as determined by high-pressure liquid chromatography. There was limited evidence that shorter treatment regimens (in particular the 1-day regimen) selected for fewer strains with reduced susceptibility. In conclusion, the 2-day treatment would overall require a shorter withholding time than the 5-day treatment and, in view of the increased peak antibiotic concentrations, may give rise to improved efficacy, in particular for treating respiratory and systemic infections. However, it would be necessary to validate the 2-day regimen in a field situation and in particular against respiratory and systemic infections to validate or refute this hypothesis.
authors.affiliation: Department of Food and Environmental Safety, Veterinary Laboratories Agency, New Haw, Surrey, KT15 3NB, United Kingdom. l.randall@vla.defra.gsi.gov.uk
authors.forename: Luke P
authors.initials: LP
authors.lastname: Randall
authors.forename: Sue W
authors.initials: SW
authors.lastname: Cooles
authors.forename: Nick C
authors.initials: NC
authors.lastname: Coldham
authors.forename: Ken S
authors.initials: KS
authors.lastname: Stapleton
authors.forename: Laura J V
authors.initials: LJ
authors.lastname: Piddock
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Woodward
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002432:Cecum / Q000382:microbiology; D015169:Colony Count, Microbial; D003510:Cyclohexanes / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D000077422:Enrofloxacin; D005243:Feces / Q000382:microbiology; D024841:Fluoroquinolones / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005798:Genes, Bacterial; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011200:Poultry / Q000382:microbiology*; D011201:Poultry Diseases / Q000188:drug therapy / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D012703:Serotyping
chemical_list: D000900:Anti-Bacterial Agents; D003510:Cyclohexanes; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D027081:DNA Gyrase