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Antimicrobial Agents and Chemotherapy, July 2008, p. 2538-2543, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00510-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Francesc Marco,¹ Cristina García de la Mària,¹ Yolanda Armero,¹ Eurídice Amat,¹ Dolors Soy,² Asunción Moreno,³ Ana del Río,³ Manel Almela,¹ Carlos A. Mestres,⁴ José M. Gatell,³ María Teresa Jiménez de Anta,¹ José M. Miró,^3* for the Hospital Clinic Experimental Endocarditis Study Group

Microbiology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain,¹ Pharmacy Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain,² Infectious Diseases Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain,³ Cardiovascular Institute, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain⁴

Received 16 April 2007/ Returned for modification 20 May 2007/ Accepted 13 April 2008

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 µg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 µg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA.

Published ahead of print on 21 April 2008.

The following are members of the Hospital Clinic Endocarditis Study Group at the Hospital Clínic-IDIBAPS, University of Barcelona School of Medicine, Barcelona, Spain: J. M. Miró, A. Moreno, A. del Río, and J. M. Gatell (Infectious Diseases Service); F. Marco, C. García de la Mària, Y. Armero, M. Almela, and M. T. Jiménez de Anta (Microbiology Service); C. A. Mestres, R. Cartañá, S. Ninot, J. L. Pomar, M. Azqueta, M. Sitges, J. C. Paré, and G. Sanz (Cardiovascular Institute); N. Pérez, J. Ramírez, and T. Ribalta (Pathology Department); M. Brunet (Toxicology Service); D. Soy (Pharmacy Service); and E. de Lazzari (UASP).