The effects of different enrofloxacin dosages on clinical efficacy and resistance development in chickens experimentally infected with Salmonella Typhimurium

Abstract

To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance of Salmonella in experimentally infected chickens and simultaneously resistance selection in Salmonella and coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal. Results showed that 100 mg/kg b.w. of enrofloxacin completely eradicated Salmonella, but resistant coliforms (4.0-60.8%) were selected from the end of the second round's withdrawal period till the end of the experiment (days 28-42). PK/PD based dosage (4 mg/kg b.w.) effectively reduced Salmonella for the first treatment duration. However upon cessation of medication, Salmonella repopulated chickens and persisted till the end with reduced susceptibility (MIC_CIP = 0.03-0.25 mg/L). Low frequency (5-9.5%) of resistant coliforms was selected (days 39-42). Enrofloxacin at dosage of 0.1 mg/kg b.w. was not able to eliminate Salmonella and selected coliforms with slight decreased susceptibility (MIC_ENR = 0.25 mg/L). In conclusion, short time treatment (7 days) of enrofloxacin at high dosage (100 mg/kg b.w.) could be effective in treating Salmonella infection while minimizing resistance selection in both Salmonella and coliforms.

Figure 1

Semilogarithmic plots of the concentrations of enrofloxacin in serum and intestinal contents in healthy and infected chickens after oral administration at a dose of 10 mg/kg b.w. Values are means ± SDs (n = 5).

Figure 2

In vitro antibacterial activity of enrofloxacin against Salmonella Typhimurium CVCC541 in MH broth.

Figure 3

Effect of different dosages of enrofloxacin on the total viable counts of Salmonella shedding from chickens. Values are means ± SDs (n = 5). Black columns represent time points for treatment durations, grey columns represent time points for withdrawal periods, striped columns represent time points prior to medication (day 0). *mean values significantly different from those for the control group (p < 0.05).

Figure 4

Effect of different dosages of enrofloxacin on resistance development in chicken fecal coliforms. (i) total counts of coliforms during experiment; (ii) levels of less susceptible (grown on MacConkey plates containing 0.125 mg/L enrofloxacin) coliforms during experiment; (iii) levels of non-susceptible (grown on MacConkey plates containing 0.25 mg/L enrofloxacin) coliforms during experiment; (iv) levels of resistant (grown on MacConkey plates containing 2 mg/L enrofloxacin) coliforms during experiment. Values are means ± SDs (n = 5). Black columns represent time points for treatment durations, grey columns represent time points for withdrawal periods, striped columns represent time points prior to medication (day 0). *mean values significantly different from those for the control group (p < 0.05).

Figure 5

Prediction of the enrofloxacin concentrations in intestinal contents of chickens treated with three dosage of enrofloxacin (blue: 0.1 mg/kg b.w.; red: 4 mg/kg b.w.; green: 100 mg/kg b.w.) by Mlxplore software. The upper window (a) shows the whole picture, the lower window (b) shows the enlarged version.