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Pharmacodynamics of a Simulated Single 1,200-Milligram Dose of Oritavancin in an In VitroPharmacokinetic/Pharmacodynamic Model of Methicillin-Resistant Staphylococcus aureusInfection
- Source :
- Antimicrobial Agents and Chemotherapy; September 2012, Vol. 57 Issue: 1 p205-211, 7p
- Publication Year :
- 2012
-
Abstract
- ABSTRACTThe safety and efficacy of a single 1,200-mg dose of the lipoglycopeptide oritavancin are currently being investigated in two global phase 3 studies of acute bacterial skin and skin structure infections. In this study, an in vitropharmacokinetic/pharmacodynamic model was established to compare the free-drug pharmacodynamics associated with a single 1,200-mg dose of oritavancin to once-daily dosing with daptomycin at 6 mg/kg of body weight and twice-daily dosing with vancomycin at 1,000 mg against three methicillin-resistant Staphylococcus aureus(MRSA) strains over 72 h. The area under the bacterial-kill curve (AUBKC) was used to assess the antibacterial effect of each dosing regimen at 24 h (AUBKC0-24), 48 h (AUBKC0-48), and 72 h (AUBKC0-72). The rapid bactericidal activities of oritavancin and daptomycin contributed to lower AUBKC0-24s for the three MRSA strains than with vancomycin (P< 0.05, as determined by analysis of variance [ANOVA]). Oritavancin exposure also resulted in a lower AUBKC0-48and AUBKC0-72against one MRSA strain and a lower AUBKC0-48for another strain than did vancomycin exposure (P< 0.05). Furthermore, daptomycin exposure resulted in a lower AUBKC0-48and AUBKC0-72for one of the MRSA isolates than did vancomycin exposure (P< 0.05). Lower AUBKC0-24s for two of the MRSA strains (P< 0.05) were obtained with oritavancin exposure than with daptomycin. Thus, the antibacterial effect from the single-dose regimen of oritavancin is as effective as that from either once-daily dosing with daptomycin or twice-daily dosing with vancomycin against the MRSA isolates tested in an in vitropharmacokinetic/pharmacodynamic model over 72 h. These results provide further justification to assess the single 1,200-mg dose of oritavancin for treatment of acute bacterial skin and skin structure infections.
Details
- Language :
- English
- ISSN :
- 00664804 and 10986596
- Volume :
- 57
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Antimicrobial Agents and Chemotherapy
- Publication Type :
- Periodical
- Accession number :
- ejs29224938
- Full Text :
- https://doi.org/10.1128/AAC.01428-12