Pharmacokinetic/pharmacodynamic integration of cefquinome against Pasteurella Multocida in a piglet tissue cage model

Abstract

To explore the in vivo antimicrobial activity of cefquinome against Pasteurella multocida in piglets, a piglet tissue cage infection model was used in this study. After the population of P.multocida reached 107 CFU/mL in a tissue cage, piglets received an intramuscular administration of cefquinome at 0.2, 0.4, 0.8, 1, 2, and 4mg/kg once daily for 3days. To assess the tissue cage pharmacokinetics (PKTCF) of cefquinome, tissue cage fluid was collected for cefquinome analysis at 1, 3, 6, 9, 12, and 24hr after each of the 3 daily drug administrations. Bacteria were counted every 24hr after drug administration and at 48 and 72hr after the last administration. Evaluation of the relationship between pharmacokinetic/pharmacodynamic (PK/PD) parameters and the antibacterial effect showed that the surrogate of %T>minimum inhibitory concentration (MIC) (R2 =0.981) was the best PK/PD index that correlated with effectiveness of cefquinome against P. multocida. The respective values of %T>MIC required for continuous 1/3-log, 1/2-log, and 1-log reductions were 14.23, 34.45, and 73.44%, respectively, during each 24-hr treatment period. In conclusion, cefquinome exhibited a potent antibacterial effect against P.multocida. When %T>MIC reached 73.44%, cefquinome exhibited a bactericidal effect against P.multocida after three successive daily administrations.