Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphylococcus aureus in a murine thigh infection model

J Antimicrob Chemother. 2003 Sep;52(3):405-11. doi: 10.1093/jac/dkg337. Epub 2003 Aug 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use*
  • Area Under Curve
  • Daptomycin / pharmacokinetics*
  • Daptomycin / therapeutic use*
  • Enterococcus / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology*
  • Methicillin Resistance*
  • Mice
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*
  • Thigh


  • Anti-Bacterial Agents
  • Daptomycin