JAC Advance Access originally published online on August 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 405-411
© 2003 The British Society for Antimicrobial Chemotherapy
Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphylococcus aureus in a murine thigh infection model
1 Center for Anti-infective Research and Development, 2 Division of Infectious Diseases and 3 Office of Research Administration, Hartford Hospital, Hartford, CT 06102, USA
Received 18 December 2002; returned 6 April 2003; revised 12 May 2003; accepted 18 May 2003
Objective: To describe the pharmacodynamic profile of daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) and Enterococci species based on bacterial density in an immunocompromised mouse thigh infection model.
Materials and methods: The pharmacodynamic (PD) profile of daptomycin was determined against two MRSA, one vancomycin-resistant Enterococcus faecium, and one vancomycin-susceptible Enterococcus faecalis using the immunocompromised murine thigh model. Efficacy was assessed by the change in log10 cfu in thighs after 24 h of drug treatment.
Results: Daptomycin produced a maximal kill of 4.5–5 log10 cfu against the MRSA and 1.5–2 log10 for the Enterococcus species. AUC/MIC was the most predictive of the PD parameters. Utilizing MICs determined in serum or broth in the calculation of the PD parameters had minimal effect on this correlation. AUCfree/MICbroth required for static effects with MRSA and Enterococcus species were 12–36 and 5–13, whereas 99% of maximal kill was achieved at ratios of 171–442 and 38–157, respectively.
Conclusions: These data reveal the potent in vivo bactericidal activity of daptomycin against MRSA and Enterococcus species using clinically achievable drug exposures (dose 4–6 mg/kg per day) currently under investigation in man.
Keywords: pharmacodynamic profiles, lipopeptides, Gram-positive organisms
* Corresponding author. Tel: +1-860-545-5567; Fax: +1-860-545-3992; E-mail: dnicola{at}harthosp.org
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