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Open Access Research article

Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients

Chung-Chih Lai1, Wang-Huei Sheng24*, Jann-Tay Wang2, Aristine Cheng3, Yu-Chung Chuang2, Yee-Chun Chen2 and Shan-Chwen Chang2

Author affiliations

1 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3 Department of Internal Medicine, Far-East Memorial Hospital, New Taipei City, Taiwan

4 Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan

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Citation and License

BMC Infectious Diseases 2013, 13:66  doi:10.1186/1471-2334-13-66

Published: 4 February 2013

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.

Keywords:
Daptomycin; High dose; Creatine phosphokinase; Treatment outcomes