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Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci

Vouillamoz, Jacques ; Moreillon, Philippe ; Giddey, Marlyse ; Entenza, José M.

In: Journal of Antimicrobial Chemotherapy, 2006, vol. 58, no. 6, p. 1208-1214

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    Titel
    • Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci
    Autor
    • Vouillamoz, Jacques. Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland
    • Moreillon, Philippe. Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland
    • Giddey, Marlyse. Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland
    • Entenza, José M.. Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Journal of Antimicrobial Chemotherapy, 2006, vol. 58, no. 6, p. 1208-1214. Oxford University Press
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:300931
    Summary
    Objectives: Daptomycin was tested in vitro and in rats with experimental endocarditis against the ampicillin-susceptible and vancomycin-susceptible Enterococcus faecalis JH2-2, the vancomycin-resistant (VanA type) mutant of strain JH2-2 (strain JH2-2/pIP819), and the ampicillin-resistant and vancomycin-resistant (VanB type) Enterococcus faecium D366. Methods: Rats with catheter-induced aortic vegetations were treated with doses simulating intravenously kinetics in humans of daptomycin (6 mg/kg every 24 h), amoxicillin (2 g every 6 h), vancomycin (1 g every 12 h) or teicoplanin (12 mg/kg every 12 h). Treatment was started 16 h post-inoculation and continued for 2 days. Results: MICs of daptomycin were 1, 1 and 2 mg/L, respectively, for strains JH2-2, JH2-2/pIP819 and D366. In time-kill studies, daptomycin showed rapid (within 2 h) bactericidal activity against all strains. Daptomycin was highly bound to rat serum proteins (89%). In the presence of 50% rat serum, simulating free concentrations, daptomycin killing was maintained but delayed (6-24 h). In vivo, daptomycin treatment resulted in 10 of 12 (83%), 9 of 11 (82%) and 11 of 12 (91%) culture-negative vegetations in rats infected with strains JH2-2, JH2-2/pIP819 and D366, respectively (P < 0.001 compared to controls). Daptomycin efficacy was comparable to that of amoxicillin and vancomycin for susceptible isolates. Daptomycin, however, was significantly (P < 0.05) more effective than teicoplanin against the glycopeptide-susceptible strain JH2-2 and superior to all comparators against resistant isolates. Conclusions: These results support the use of the newly proposed daptomycin dose of 6 mg/kg every 24 h for treatment of enterococcal infections in humans