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Antimicrobial Agents and Chemotherapy, February 2001, p. 454-459, Vol. 45, No. 2
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.2.454-459.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Bactericidal Activities of Two Daptomycin Regimens against Clinical Strains of Glycopeptide Intermediate-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations

Ronda L. Akins1,2,dagger and Michael J. Rybak1,2,3,*

The Anti-Infective Research Laboratory, Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center,1 and the College of Pharmacy and Allied Health Professions2 and School of Medicine,3 Wayne State University, Detroit, Michigan 48201

Received 31 May 2000/Returned for modification 11 August 2000/Accepted 1 November 2000

Daptomycin is an investigational lipopeptide antibiotic active against gram-positive organisms. The mechanism of action is unique, resulting in interference with cell membrane transport. The bactericidal activity of daptomycin was evaluated against glycopeptide-intermediate susceptible Staphylococcus aureus (GISA), vancomycin-resistant Enterococcus faecium (VREF), and methicillin-resistant S. aureus (MRSA) in an in vitro infection model with simulated endocardial vegetations. Simulated regimens of daptomycin at 6 mg/kg/day (D6) and 10 mg/kg/day (D10) were utilized. MICs and MBCs for daptomycin were determined in the absence and in the presence of albumin with the following results (MIC/MBC): for GISA-992, 0.5/1.0 and 16/16; for VREF-590, 2.0/2.0 and 32/32; and for MRSA-494, 0.25/0.25 and 1.0/4.0 µg/ml, respectively. During the first 8 h daptomycin significantly reduced the inoculum for all organisms. Daptomycin at 6 mg/kg/day and 10 mg/kg/day had log10 CFU/g reductions of 5 and 6, 3.4 and 5, and 6.4 and 6.5 by 8 h for GISA-992, VREF-590, and MRSA-494, respectively. Against both GISA-992 and VREF-590, the D10 regimen achieved the limit of detection at 72 h, with D6 regimens showing slight regrowth. A concentration-dependent killing effect was noted to occur, with daptomycin demonstrating a more rapid and greater kill from the D10 versus the D6 regimen. The results of this study suggest that daptomycin demonstrates significant (P < 0.05) activity against gram-positive organisms in a simulated sequestered infection site.

* Corresponding author. Mailing address: The Anti-Infective Research Laboratory, Department of Pharmacy Services (1B), Detroit Receiving Hospital and University Health Center, 4201 St. Antoine Blvd., Detroit, MI 48201. Phone: (313) 745-4554. Fax: (313) 993-2522. E-mail: m.rybak{at}wayne.edu.

dagger Present address: School of Pharmacy, Department of Pharmacy Practice, Texas Tech University, Amarillo, TX 79106.

Antimicrobial Agents and Chemotherapy, February 2001, p. 454-459, Vol. 45, No. 2
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.2.454-459.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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