Daptomycin Alone and in Combination with Rifampin for the Treatment of Experimental Methicillin-Resistant Staphylococcus aureus (MRSA) Implant-Associated Infection

Background: We investigated the in-vitro susceptibility, pharmacokinetics and treatment efficacy of daptomycin (DAP), alone and in combination with rifampin (RIF), compared to vancomycin (VAN), in a foreign-body MRSA infection model. Methods: MRSA (ATCC 43300) MIC and MBC was determined in growth media supplemented with 50 mg/l Ca2+. In guinea pigs 4 Teflon cages were s.c. implanted. Pharmacokinetics was determined in sterile cage fluid after a single i.p. dose of DAP using a bioassay. Cages were inoculated with 2.9 x 106 cfu MRSA. After 3 days of infection, i.p. treatment was started for 4 days. Bacteria were determined in cage fluid during and 5 days after treatment (12 cages/regimen). Cages were then explanted and cultured in TSB to detect adherent bacteria. Emergence of RIF resistance was tested by plating cage cultures on agar plates containing 1 µg/ml RIF. Results: MIC, MBClog and MBCstat of DAP (µg/ml) were 0.625, 0.625 and 20, respectively. After single dose of 20, 30 and 40...