title: Efficacy of daptomycin versus vancomycin in an experimental model of foreign-body and systemic infection caused by biofilm producers and methicillin-resistant Staphylococcus epidermidis.
abstract: 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 biofilm-producing methicillin-resistant S. epidermidis.
authors: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, and Institute of Biomedicine of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. judoher@yahoo.es
authors: J
authors: J
authors: Domínguez-Herrera
authors: F
authors: F
authors: Docobo-Pérez
authors: R
authors: R
authors: López-Rojas
authors: C
authors: C
authors: Pichardo
authors: R
authors: R
authors: Ruiz-Valderas
authors: J A
authors: JA
authors: Lepe
authors: J
authors: J
authors: Pachón
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002408:Catheters, Indwelling / Q000382:microbiology; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008099:Liver / Q000382:microbiology; D016106:Methicillin Resistance / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests / Q000592:standards; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin