Pharmacokinetics in foremilk and antimicrobial activity of cephapirin following intramammary administration in healthy and Staphylococcus aureus-infected cows

Abstract

AIM: To evaluate the kinetic profile of cephapirin and detect differences in its milk disposition following intramammary administration in healthy, and subclinically Staphylococcus aureus infected, quarters of lactating cows, to assess the minimum inhibitory concentration (MIC) of cephapirin for Staph. aureus field isolates, and to calculate the time during which drug concentrations were above the MIC (T>MIC).

METHODS: Five healthy and five Staph. aureus-infected lactating cows received cephapirin at 275 mg/quarter, twice at 12-hour intervals. Foremilk samples were manually collected from individual quarters before treatments and 2, 8, 12 hours after the last drug administration, and then every 12 hours until the tenth milking. Concentrations of cephapirin and desacetyl-cephapirin were measured in milk samples after solid phase extraction and high-performance liquid chromatography analysis. A non-compartmental model was applied to data to obtain pharmacokinetic results. Eleven Staph. aureus isolates from the study-infected quarters and 30 additional isolates from cows in another two farms in the same area were used to determine MIC for cephapirin using the microdilution broth method.

RESULTS: Mean maximum drug concentrations were higher in milk from healthy quarters (1334.8 (SD 1322.7) µg/mL) than in the infected ones (234.7 (SD 141.4) µg/mL), but the elimination half-life was longer in the infected (4.8 (SD 1.9) hours) than uninfected (3.3 (SD 0.33) hours) quarters (p<0.05). Mean residence time was comparable in healthy and infected quarters (approximately 8 hours). The amounts of desacetyl-cephapirin recovered in the samples were very low (below 2%). The MIC₉₀ for all field strains of Staph. aureus (n=41) was 0.25 μg/mL. The calculated T>MIC₉₀ was 38 (SD 13), 27 (SD 11) and 35 (SD 8) hours after last treatment in healthy, suspected and infected quarters, respectively.

CONCLUSION AND CLINICAL RELEVANCE: The intramammary administration of sodium cephapirin at 275 mg/quarter, twice every 12 hours in lactating cows resulted in higher drug concentrations in milk of quarters with no infection than in the subclinically infected ones. These concentrations were above the MIC₉₀ for 35 hours in infected cows. According to these results intramammary administration of cephapirin at 12-hour intervals during lactation should be potentially effective against Staph. aureus infection, but studies of clinical efficacy are necessary for confirmation.

KEY WORDS:

• cephapirin
• subclinical mastitis
• Staphylococcus aureus
• intramammary
• pharmacokinetics
• pharmacodynamics
• dairy cows

Acknowledgements

The authors kindly thank Dr. Rosangela Garlappi for her willingness and her precious assistance during the study, Intervet International BV and Fatro S.p.A. for the supply of the analytical standards and the veterinary product, respectively.