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
Yoshio Takesue, Hiroshige Mikamo, Shinya Kusachi, Shinichi Watanabe, Kenichi Takahashi, Tomoko Yoshinari, Mikio Ishii, Naoki Aikawa, Yoshio Takesue, Hiroshige Mikamo, Shinya Kusachi, Shinichi Watanabe, Kenichi Takahashi, Tomoko Yoshinari, Mikio Ishii, Naoki Aikawa
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.
Trial registration: ClinicalTrials.gov NCT00770341.
Keywords: Creatine phosphokinase; Daptomycin; Methicillin-resistant Staphylococcus aureus; Pharmacokinetics; Skin and soft tissue infection.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed