Daptomycin is effective in treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus.
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 microg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 microg/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.
Marco
Francesc
F
Microbiology Service, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi-Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain.
de la Mària
Cristina García
CG
Armero
Yolanda
Y
Amat
Eurídice
E
Soy
Dolors
D
Moreno
Asunción
A
del Río
Ana
A
Almela
Manel
M
Mestres
Carlos A
CA
Gatell
José M
JM
Jiménez de Anta
María Teresa
MT
Miró
José M
JM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017576:Daptomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006020:Glycopeptides / Q000627:therapeutic use; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D014640:Vancomycin; D017576:Daptomycin