PK/PD of cefoperazone after intramammary administration in healty and mastitic (subclinical Staphilococcus aureus) lactating cows

Cefoperazone (CFP) is a 3rd generation cephalosporin commonly used for treatment of bovine mastitis sustained by Staphylococcus spp., Streptococcus spp. and Escherichia coli. The CFP kinetic profile in milk after single intramammary administration (300 mg/quarter) in healthy and subclinical mastitic lactating cows and the MIC values for Staph. aureus were determined to carry out the PK/PD evaluation. The serum concentrations were evaluated to assess the potential absorption differences between health and mastitic animals. After treatment, milk samples were obtained from each quarter from 30 min until the 10th milking, while serum samples were collected in the 24 hours post-administration. CFP was quantified by an HPLC validated method (LOQ = 0.01 g.mL-1). CFP was detected in milk samples till the 5-6th milking. In serum CFP concentrations were close to LOQ in healthy animals (range 0.01-0.03 g.mL-1) and slightly higher in mastitic animals (range 0.01-0.17 g.mL-1). The low serum concentrations did not allow the pharmacokinetic analysis and confirmed the scarce absorption after intramammary administration. CFP MIC50 and MIC90 determined for Staph. aureus (field strains n=24) were 0.5 and 0.64 g.mL-1, respectively. Considering that T>MIC (time that concentrations exceed the MIC) is the PK/PD index for cephalosporins efficacy and the results obtained, 50±11.8 and 58±14.03 hours in healthy and infected animals, respectively, it is possible to foresee a good efficacy for about 4-5 milkings when CFP is administered intramammary at the dose of 300 mg/quarter in mastitic cows.