title: Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections.
abstract: Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.
authors.affiliation: Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Kusachi
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takesue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Morita
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsumori
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kato
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshinari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D017576:Daptomycin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine; D017576:Daptomycin