PK/PD approach to evaluate two oral administration routes of flumequine and enrofloxacin in turkey

Individualization of therapy is one of the major goal to limit the spread of antibiotic resistance, unfortunately avian species and turkeys in particular, are generally treated via medicated water or feed and this approach is at the opposite site of an individualized treatment. The bolus administration via gavage is not commonly used in turkey breeding but assures the achievement of maximum drugs concentrations in a short time and also exclude behavioral influences in the drugs administration, as water palatability, thirst, hierarchy. In the avian clinical practice a 10 h pulsed medication is a frequent dosage scheme, that can be easily handled by the farmers and assures the complete drugs administration in a limited period of time. Flumequine (FLU) and enrofloxacin (ENRO) are 1st and 2nd generation quinolones commonly used in food-producing species to control infection caused by various Gram-negative bacteria. FLU is still employed in several animal species for its relative low cost and good tolerability, whereas ENROs use is limited to valuable food and companion animals. To evaluate the effectiveness of the authorized EU dosage of FLU and ENRO against zoonotic avian pathogens, the kinetic results after bolus and 10 h pulsed administration were correlated with the MICs50 determined by the broth microdilution method in 210 E. coli strains isolated from poultry in Italy. For FLU the mean Cmax/MIC and AUC0-24/MIC were 0.67±0.09 and 4.76±0.48 for the bolus administration and 0.30±0.08 and 3.22±0.93 for the 10 h pulsed administration. For ENRO the mean Cmax/MIC and AUC0-24/MIC were 3.07±0.62 and 25.48±3.04 for the bolus administration and 1.35±0.37 and 15.31±2.92 for the 10 h pulsed administration. Both drugs and type of administrations gave unsatisfactory results. Especially, the 10 h pulsed medicated water, that is frequently used, but do not allow to reach efficacious concentrations against E. coli. The results indicate that the authorised EU dosage of FLU and ENRO are not effective against E. coli and could contribute to the diffusion of antibiotic resistance.