Daptomycin Is Effective in the Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus

Microbiology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain; Pharmacy Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain; Infectious Diseases Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain; Cardiovascular Institute, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain

^* To whom correspondence should be addressed. Email: jmmiro{at}ub.edu.

	Abstract

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including S. aureus. This study evaluated in vitro and in vivo efficacy of daptomycin against 2 methicillin-resistant clinical S. aureus (MRSA) isolates: MRSA 277 (vancomycin MIC 2 µg/ml) and GISA ATCC 700788 (vancomycin MIC 8 µg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these 2 strains. The in vivo activity of daptomycin (6 mg/kg q 24 h) was evaluated using a rabbit model of infective endocarditis and compared with high-dose (HD, 1 g i.v. q 6 h) and recommended-dose (RD, 1 g i.v. q 12 h) vancomycin regimens for 48 hours and an untreated control group. Daptomycin was significantly more effective than vancomycin-RD in reducing the density of bacteria in the vegetations for the MRSA (0 [0-1.5] vs. 2 [0-5.6] log CFU/g veg; P = 0.02) and GISA (2 ([0-2]) vs. 6.6 [2.0-6.9] log CFU/g veg; P < 0.01) strains studied. In addition, daptomycin sterilized more vegetations than vancomycin-RD against MRSA (13/18 [72%] vs. 7/20 [35%]; P = 0.02) and both vancomycin regimens against GISA (12/19 [63%] vs. 4/20 [20%]; P < 0.01). No statistical difference between vancomycin-HD and vancomycin-RD for MRSA treatment was noted. These results support the use of daptomycin for treatment of aortic valve endocarditis caused by GISA and MRSA.