title: Efficacy of topical and systemic antibiotic treatment of meticillin-resistant Staphylococcus aureus in a murine superficial skin wound infection model.
abstract: Meticillin-resistant Staphylococcus aureus (MRSA) is a rapidly spreading pathogen associated predominantly with skin infections. The lack of clinical evidence indicating the best treatment strategy to combat MRSA skin infections prompted us to investigate the efficacy of available treatment options in an experimental skin wound infection model in mice. Mice were treated either topically with retapamulin (1%), fusidic acid (2%) or mupirocin (2%) or systemically with linezolid (50-100 mg/kg/day) or vancomycin (50-200 mg/kg/day) twice daily for 3 days or 6 days and the total bacterial loads in the skin lesions were determined. Retapamulin, fusidic acid and mupirocin treatment for 3 days reduced the bacterial loads by 2.5, 2.9 and 2.0 log(10) CFU, respectively, and treatment for 6 days by 5.0, 4.2 and 5.1 log(10) CFU, respectively, compared with non-treated controls (P < 0.001). Systemic treatment with linezolid for 6 days reduced the bacterial loads by 1.6 log(10) CFU compared with non-treated mice (P < 0.001), whereas vancomycin treatment showed no effect on reducing the bacterial loads in infected skin lesions. These findings suggest that topical treatment with retapamulin and mupirocin is significantly more effective than systemic treatment with linezolid and vancomycin in eradicating MRSA in skin wounds. Retapamulin and mupirocin may provide an alternative to fusidic acid treatment of MRSA in skin wounds when resistance to fusidic acid is suspected.
authors.affiliation: Microbiology & Infection Control, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. cvl@ssi.dk
authors.forename: Carina
authors.initials: C
authors.lastname: Vingsbo Lundberg
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Møller
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D058491:Bacterial Load / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D004224:Diterpenes; D005260:Female; D005672:Fusidic Acid / Q000627:therapeutic use; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000627:therapeutic use; D023303:Oxazolidinones / Q000627:therapeutic use; D013207:Staphylococcal Skin Infections / Q000188:drug therapy*; D014640:Vancomycin / Q000627:therapeutic use; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004224:Diterpenes; D023303:Oxazolidinones; C508887:retapamulin; D005672:Fusidic Acid; D014640:Vancomycin; D016712:Mupirocin; D000069349:Linezolid
keywords: In vivo; MRSA; Mouse models; Topical agents; USA300