Efficacy of lincosaminide antibiotics in the treatment of experimental staphylococcal mastitis in lactating mice

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Abstract
Staphylococcus aureus is a frequent cause of bovine mastitis worldwide. A model that may predict the efficacy of antimicrobial agents in the treatment of bovine mastitis induced by Staph. aureus was developed in lactating mice. Infection was established by the inoculation of lactating CF1 mice with Staph aureus into the mammary gland via the teat duct. At the dose of bacteria used, 85–90% of the inoculated, untreated animals developed a nonlethal, acute mastitis within 48 h. Antibiotic treatment was administered subcutaneously or by the intramammary route. Lincosaminide antibiotics including lincomycin, clindamycin, and pirlimycin were evaluated in this system. Other compounds which have been used in therapy of bovine mastitis including novobiocin, penicillin G, ampicillin, cloxacilhn and rifamycin-SV were used as reference antibiotics. Pirlimycin was the most effective of the antibiotics tested in this standardized system. Depending upon the route of administration, this novel lincosaminide was 15 to 95-fold more effective than clindamycin, three- to six-fold better than lincomycin, two- to ten-fold more effective than novobiocin, 13- to 17-times more effective than cloxacillin and 8- to 22-times better than nfamycin-SV on a weight-dose comparison. Penicillin G and ampicillin were the least effective drugs tested against mastitis induced by the β-lactamase producing strain of Staph. aureus used in these assays. Pharmacokinetic experiments suggested that the greater effectiveness of pirlimycin compared to clindamycin and lincomycin was due to increased affinity for and prolonged retention in the mammary gland