Bactericidal activity of daptomycin against vancomycin-resistant Enterococcus faecium in an in vitro pharmacokinetic model.
A dynamic in vitro model was used to determine the killing kinetics of daptomycin against 15 vancomycin-resistant clinical isolates of Enterococcus faecium. Concentration profiles simulating those observed in serum following administration of both low-dose (2 mg/kg) and high-dose (6 mg/kg) daptomycin were bactericidal within 5.5 and 2.8 h, respectively. In contrast, when albumin was added to the growth medium, the corresponding bacterial killing times were slowed to greater than 24 h and 7 h; these results suggest that in the clinical setting, daptomycin dosages of approximately 6 mg/kg are required to achieve bactericidal activity against vancomycin-resistant Enterococcus faecium.
Bingen
E
E
Laboratoire de Microbiologie, Hôpital Robert Debré, Paris, France.
Doit
C
C
Lambert-Zechovsky
N
N
Tod
M
M
Petitjean
O
O
Bourgeois
F
F
Mariani-Kurkdjian
P
P
D000418:Albumins / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D017576:Daptomycin; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010455:Peptides / Q000097:blood / Q000494:pharmacology; D015610:Serum Bactericidal Test; D014640:Vancomycin / Q000097:blood / Q000494:pharmacology*
D000418:Albumins; D000900:Anti-Bacterial Agents; D010455:Peptides; D014640:Vancomycin; D017576:Daptomycin