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: Chung-Chih Lai, Wang-Huei Sheng, Jann-Tay Wang, Aristine Cheng, Yu-Chung Chuang, Yee-Chun Chen, Shan-Chwen Chang
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 13 Pg. 66 (Feb 04 2013) ISSN: 1471-2334 [Electronic] England
• PMID: 23379510 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Daptomycin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, adverse effects, therapeutic use)
• Daptomycin (administration & dosage, adverse effects, therapeutic use)
• Female
• Gram-Positive Bacteria (classification, drug effects)
• Gram-Positive Bacterial Infections (drug therapy)
• Humans
• Inpatients
• Male
• Middle Aged
• Retrospective Studies
• Salvage Therapy
• Sepsis (drug therapy)
• Treatment Outcome
• Young Adult