Correlation between pharmacokinetic/pharmacodynamic indices and clinical outcomes in Japanese patients with skin and soft tissue infections treated with daptomycin: analysis of a phase III study.

Abstract

The relationships between pharmacokinetic (PK)/pharmacodynamic (PD) indices and outcomes were investigated in patients with skin and soft tissue infection (SSTI) who received daptomycin at 4 mg/kg/day. Efficacy was evaluated in 55 patients from whom Staphylococcus aureus was isolated, with success rates of 94.5% and 69.1% for clinical and microbiological responses, respectively. The odds ratio for the relationship between the area under the day 1 concentration-time curve (AUC0-24h) to the MIC and the probability of clinical success was 1.03 (95% confidence interval [CI] 0.73-1.45), and that for the relationship for probability of microbiological success was 0.94 (95% CI 0.81-1.09). In 82 patients in the safety analysis, only 1 met the creatine phosphokinase (CPK) elevation criteria, and this patient's minimum concentration (C(min)) of plasma daptomycin was 5.37 μg/mL. No significant relationship was found between peak CPK and C(min) (Pearson's correlation coefficient -0.0452). In conclusion, no clear correlation between PK/PD indices and the probability of efficacy or safety events was demonstrated when daptomycin was administered in SSTI patients using the clinically recommended dosage of 4 mg/kg/day.

• Authors: Yoshio Takesue, Hiroshige Mikamo, Shinya Kusachi, Shinichi Watanabe, Kenichi Takahashi, Tomoko Yoshinari, Mikio Ishii, Naoki Aikawa
• Journal: Diagnostic microbiology and infectious disease (Diagn Microbiol Infect Dis) Vol. 83 Issue 1 Pg. 77-81 (Sep 2015) ISSN: 1879-0070 [Electronic] United States
• PMID: 26072149 (Publication Type: Clinical Study, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Daptomycin

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Asian People
• Daptomycin (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Female
• Humans
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Soft Tissue Infections (drug therapy)
• Staphylococcal Skin Infections (drug therapy)
• Staphylococcus aureus (drug effects, isolation & purification)
• Treatment Outcome
• Young Adult