Staphylococcus epidermidis is a frequent cause of device-associated infections. In this study, we compared the efficacy of daptomycin versus vancomycin against biofilm-producing methicillin-resistant S. epidermidis (MRSE) strains in a murine model of foreign-body and systemic infection. Two bacteremic biofilm-producing MRSE strains were used (SE284 and SE385). The MIC of daptomycin was 1 mg/liter for both strains, and the MICs of vancomycin were 4 and 2 mg/liter for SE284 and for SE385, respectively. The in vitro bactericidal activities of daptomycin and vancomycin were evaluated by using time-kill curves. The model of foreign-body and systemic infection of neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n ؍ 15): without treatment (controls) or treated with daptomycin at 50 mg/kg/day or vancomycin at 440 mg/kg/day. In vitro, daptomycin showed concentration-dependent bactericidal activity, while vancomycin presented time-dependent activity. In the experimental in vivo model, daptomycin and vancomycin decreased liver and catheter bacterial concentrations (P < 0.05) and increased the survival and the number of sterile blood cultures (P < 0.05) using both strains. Daptomycin produced a reduction in the bacterial liver concentration higher than 2.5 log 10 CFU/g compared to vancomycin using both strains, with this difference being significant (P < 0.05) for infection with SE385. For the catheter bacterial concentrations, daptomycin reduced the concentration of SE284 3.0 log 10 CFU/ml more than did vancomycin (P < 0.05). Daptomycin is more effective than vancomycin for the treatment of experimental foreign-body and systemic infections by biofilmproducing methicillin-resistant S. epidermidis.
Staphylococcus epidermidis is a common nosocomial and health care-associated pathogen in several infections, causing important morbidity, mortality, and/or health care costs. Thus, it is the most important cause of infections of orthopedic prostheses, accounting for approximately 40% of all cases, and between 30% and 50% of catheter-related bacteremias are caused by coagulasenegative Staphylococcus (CNS) strains (19,26). Other severe and/or frequent nosocomial and health care-associated infections are also caused by CNS, being the etiology in the 22.7% of endocarditis infections (9, 13) and in 37 to 78% of cerebrospinal fluid shunt-associated infections (4, 11).Moreover, the high frequency of methicillin-resistant S. epidermidis (MRSE) is an important therapeutic problem.