Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant...

We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log₁₀ CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log₁₀ CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.