Pharmacokinetic/Pharmacodynamic Analysis of the Activity of Cefquinome when used to treat Streptococcus agalactiae in a Murine Mastitis Model

Abstract

Background: Cefquinome is a new generation of cephalosporins for animals. It has an excellent effect on the treatment of mastitis in animals. We evaluated the associations between the specific pharmacokinetic/pharmacodynamic (PK/PD) of cefquinome and its antibacterial activity against Streptococcus agalactiae in a mouse model of mastitis. After a single dose of intramammary administration of cefquinome[Concentrations: 30, 60, 120, and 240 μg/mammary gland(MG)], the concentration of cefquinome in plasma was analysed via liquid chromatography with tandem mass spectrometry (HPLC/MS–MS). PK parameters were calculated using a one-compartment first-order absorption model. Antibacterial activity was defined as the maximum change in the S. agalactiae population after each dose. Then, an inhibitory sigmoid Emax model was employed for evaluating the relationships between PK/PD index values and antibacterial effects.Results: The duration for which the concentration of the antibiotic (%T) remained above the minimum inhibitory concentration (MIC) was the optimal PK/PD index for assessing antibacterial activity. The values of %T > MIC to reach 0.5-log10 CFU/MG reduction, 1-log10 CFU/MG reduction, and 2-log10 CFU/MG reduction were 31, 47, and 81%, respectively.Conclusions: These findings provide a valuable basis for optimising dosage regimens when using cefquinome to treat S. agalactiae infections.