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 1 mg/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 14.10 h after intravenous and 14.46 h after intramuscular dosing, indicating a likely high level of effectiveness in clinical infections caused by P. multocida of MIC 0.04 μg/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.

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

“…Pharmacokinetic properties of cefquinome have been studied previously in the serum of cattle after intravenous administration at 1 mg/kg (Shan et al, 2014). The reported terminal half life, clearance and Vss were respectively 2.4 ± 0.21 h, 0.11 ± 0.03 L/h.kg, 0.3 ± 0.5 L/kg and were very close to our values.…”

“…A 10 μL volume of bacterial culture in stationary phase was added to 1 mL of serum to give a final suspension of approximately 10 6 cfu/mL. The tubes containing bacterial culture and serum were than incubated at 37°C, and viable counts were determined at 0, 2, 5, 8, and 24 h (Shan et al, 2014). …”

“…This drug has been developed especially for use in veterinary medicine (Smiet et al, 2012; Papich, 2014), and is registered in many countries worldwide. Cefquinome has been used for the treatment of many diseases including acute mastitis, respiratory diseases, food rot in cattle, calf septicemia, metritis-mastitits-agalactia syndrome in sows, foal septicemia and respiratory diseases in horses (Uney et al, 2011; Liu et al, 2012; Dumka et al, 2013; Shan et al, 2014). The advantages of cefquinome include broad spectrum antibacterial activity, stability against β-lactamase, enhanced potency, and bioavailability and the ability to penetrate easily into gram negative bacteria (Dumka et al, 2013).…”

“…The advantages of cefquinome include broad spectrum antibacterial activity, stability against β-lactamase, enhanced potency, and bioavailability and the ability to penetrate easily into gram negative bacteria (Dumka et al, 2013). Cefquinome pharmacokinetics (PK) have been studied in several animal species such as camels, horses, ducks, cows, wild boars, piglet, rabbits and cattle (Allan and Thomas, 2003; Ehinger et al, 2006; Li et al, 2008; Al-Taher, 2010; Hwang et al, 2011; Liguo et al, 2011; Liu et al, 2012; Shan et al, 2014). …”

In vitro susceptibility of four antimicrobials against Riemerella anatipestifer isolates: a comparison of minimum inhibitory concentrations and mutant prevention concentrations for ceftiofur, cefquinome, florfenicol, and tilmicosin

“…By integrating our results with the published pharmacokinetic data of antimicrobials in ducks, serum drug concentrations of cefquinome and florfenicol may fall within the MSW and the high MPC values could hardly be attained albeit these two drugs had excellent MIC values. As cephalosporin exhibited time-dependent property, we applied this approach in our study and the predicted T  > MIC was approximately 7.6 h (Table 3), which was lower than that obtained previously using P. multocida in yellow cattle [46], but slightly higher than that calculated using canine E. coli [50]. In vivo antimicrobial efficacy of cefquinome against R. anatipestifer should be further addressed.…”