title: Influence of daptomycin on staphylococcal abscesses and experimental tobramycin nephrotoxicity.
abstract: The antibacterial efficacies of daptomycin and vancomycin were compared in male Fischer rats with subcutaneous abscesses caused by either methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA). The influence of daptomycin on tobramycin nephrotoxicity was also assessed. MSSA or MRSA abscesses were treated with subcutaneous daptomycin (10 mg/kg every 12 h), vancomycin (125 mg/kg every 12 h), or diluent (every 12 h) for 5 to 10 days. Rats in both antibiotic treatment groups had lower abscess bacterial counts than did controls at days 5 and 10 (P less than 0.0025). The daptomycin treatment groups had lower abscess bacterial counts than did the vancomycin treatment groups for MSSA at day 5 (P less than 0.0025) and day 10 (P less than 0.025) and for MRSA at day 10 (P less than 0.0025). Nephrotoxicity treatment groups included animals treated for 3, 7, 10, 14, and 17 days with subcutaneous diluent (every 12 h), daptomycin (20 mg/kg every 12 h), tobramycin (40 mg/kg every 12 h), and the combination of daptomycin and tobramycin. Compared with controls, animals treated with daptomycin alone exhibited no detectable nephrotoxicity. Rats given tobramycin alone developed functional and histopathologic abnormalities from days 7 through 17. Animals treated with daptomycin and tobramycin for 14 days had a lower mean concentration of creatinine in serum (P less than 0.005), higher mean creatinine clearance values (P less than 0.05), and less cortical tubular cell regeneration (P less than 0.05) than did rats treated with tobramycin alone. In rats with staphylococcal subcutaneous abscesses, daptomycin was superior to vancomycin in treating both MSSA and MRSA. Daptomycin alone caused no detectable renal injury, and in rats given daptomycin combined with tombramycin, there was less histologic and functional renal injury than in animals given tobramycin alone.
authors.affiliation: Chiles Research Institute, Providence Medical Center, Portland, Oregon 97213.
authors.forename: C A
authors.initials: CA
authors.lastname: Wood
authors.forename: H C
authors.initials: HC
authors.lastname: Finkbeiner
authors.forename: S J
authors.initials: SJ
authors.lastname: Kohlhepp
authors.forename: P W
authors.initials: PW
authors.lastname: Kohnen
authors.forename: D N
authors.initials: DN
authors.lastname: Gilbert
mesh_terms: D000038:Abscess / Q000188:drug therapy* / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017576:Daptomycin; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008712:Methicillin / Q000494:pharmacology; D010403:Penicillin Resistance; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013997:Time Factors; D014031:Tobramycin / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D017576:Daptomycin; D008712:Methicillin; D014031:Tobramycin