| Title | Activity of daptomycin and vancomycin alone and in combination with rifampin and gentamicin against biofilm-forming MRSA in an experimental model of endocarditis. | | Author(s) | Laplante KL, Woodmansee S | | Institution | University of Rhode Island, Department of Pharmacy Practice, Infectious Diseases Research Laboratory, Providence Veterans Affairs Medical Center, Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Providence, RI. | | Source | Antimicrob Agents Chemother 2009 Jun 29. | | Abstract | Clinical and in vitro research support the theory that infective endocarditis (IE)-causing bacteria form biofilms and that biofilms negatively affect treatment outcomes. The purpose of this study was to quantify biofilm formation of methicillin resistant Staphylococcus aureus (MRSA) isolates obtained from patients infected with IE and to evaluate the in vitro activity of daptomycin and vancomycin alone and in combination with rifampin or gentamicin, while monitoring for the development of resistance. A high inoculum stationary phase infection model of IE was used to simulate human pharmacokinetics of daptomycin 6mg/kg/day, vancomycin 1.25g q12h alone and in combination with rifampin 300mg q8h, and gentamicin 1.3 mg/kg q12h. Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. Time to bactericidal activity in the presence of daptomycin was isolate dependent, but was achieved by 24h for both MRSA isolates. Vancomycin did not reach bactericidal activity throughout the experiment. At 24, 48 and 72h, daptomycin-containing regimens had significantly more activity (decline in the mean CFU/g) than any of the vancomycin-containing regimens (P=0.03). Rifampin (against MRSA B346846) and gentamicin (against both isolates) antagonized or delayed the bactericidal activity of daptomycin in the first 24h. An increase in daptomycin or vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24h. Biofilm formation increases the likelihood of antimicrobial resistance and reduces antibactericidal activity. Further investigations are needed to understand the initial delay of bactericidal activity observed when gentamicin or rifampin was combined with daptomycin. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19564363 |
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