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 4mg/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 (AUC 0–24h ) 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 5.37μg/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 4mg/kg/day.