Medication regimen for prevention of drug resistance using enroflox-acin against <I>Aeromonas hydrophilain</I> crucian carp <I>Carassius auratus</I>

Abstract

The widespread use of antibiotics in aquaculture has led to increasing problems caused by bacterial re-sistance.Given this,there is an urgent need to develop a medication regimen that prevents the formation of drug resistant bacteria.We estimated a number of pharmacodynamic(including mutant prevent concentration and mu-tant selection window) and pharmacokinetic parameters for the antibiotic drug enrofloxacin.Our objective was to develop a medication regimen against hemorrhagic septicemia in crucian carp(Carassius auratus),a disease caused by Aeromonas hydrophila.The minimal inhibitory concentration(MIC) was 0.125 μg/mL,the post-antibiotic effect(PAE) of enrofloxacin on the pathogenic bacterial strains was observed up to(1.67±0.42) h,(2.03±0.17) h,and(2.38±0.06) h at 2MIC,4MIC,and 8MIC,respectively,the mutant prevention concentration(MPC) was 1.125 μg/mL,and the mutant selection window was between 0.125 and 1.125 μg/mL.We developed integrated enrofloxacin concentration-time curves for the serum of crucian carp following administration of a range of doses.Enrofloxacin persisted in the serum at concentrations above the MPC for 5 h at a dose of 5 mg/kg;9.5 h at a dose of 10 mg/kg,and 23 h at a dose of 20 mg/kg.The serum PK/PD parameters AUC24/MIC and Cmax/MIC were 137.22 and 15.05,respectively,at a dose of 5 mg/kg,285.25 and 41.43,respectively,at a dose of 10 mg/kg,and 426.25 and 52.32,respectively,at a dose of 20 mg/kg.The drug remained in the plasma with a concentration MPC for(24-PAE) h and AUC24/MIC≥100 or Cmax/MIC8.Our results suggest that hemorrhagic septicemia can be controlled using a dosing regimen of 20 mg/kg enrofloxacin,at intervals of 24 h.The proposed withdrawal time in crucian carp should not be less than 25 d.The methods described in this study also can be used for developing dose guidelines for other anti-bacterial drugs to prevent selection for drug-resistance.