title: Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients.
abstract: BACKGROUND
  Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.
  
  
  METHODS
  A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.
  
  
  RESULTS
  A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3-53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.
  
  
  CONCLUSIONS
  Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chung-Chih
authors: CC
authors: Lai
authors: Wang-Huei
authors: WH
authors: Sheng
authors: Jann-Tay
authors: JT
authors: Wang
authors: Aristine
authors: A
authors: Cheng
authors: Yu-Chung
authors: YC
authors: Chuang
authors: Yee-Chun
authors: YC
authors: Chen
authors: Shan-Chwen
authors: SC
authors: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006094:Gram-Positive Bacteria / Q000145:classification / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
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