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


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.
Dandekar
Prachi K
PK
Center for Anti-infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.
Tessier
Pamela R
PR
Williams
Peter
P
Nightingale
Charlie H
CH
Nicolau
David P
DP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D017576:Daptomycin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016983:Enterococcus / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013848:Thigh
D000900:Anti-Bacterial Agents; D017576:Daptomycin