Pharmacokinetic/pharmacodynamic relationship of cefquinome against Pasteurella multocida in a tissue-cage model in yellow cattle

Abstract

The cephalosporin antimicrobial drug cefquinome was administered to yellow cattle intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1mg/kg of body weight in a two-period crossover study. The pharmacokinetic (PK) properties of cefquinome in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied using a tissue-cage model. The in vitro and ex vivo activities of cefquinome in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (P.multocida) were determined. A concentration-independent antimicrobial activity of cefquinome was confirmed for levels lower than 4×MIC. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the time that drug levels remain above the MIC (T>MIC) in serum was 14.10h after intravenous and 14.46h after intramuscular dosing, indicating a likely high level of effectiveness in clinical infections caused by P.multocida of MIC 0.04μg/mL or less. These data may be used as a rational basis for setting dosing schedules, which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.