title: 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.affiliation: Department of Infection Control and Prevention, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: takesuey@hyo-med.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takesue
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.affiliation: Department of Surgery, Toho University Medical Center Ohashi Hospital, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kusachi
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshinari
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D044466:Asian People; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018461:Soft Tissue Infections / Q000188:drug therapy; D013207:Staphylococcal Skin Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
keywords: Creatine phosphokinase; Daptomycin; Methicillin-resistant Staphylococcus aureus; Pharmacokinetics; Skin and soft tissue infection