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Adv Ther. 2015 Dec;32(12):1192-205. doi: 10.1007/s12325-015-0267-4. Epub 2015 Nov 26.

Evaluation of Effectiveness and Safety of High-Dose Daptomycin: Results from Patients Included in the European Cubicin(®) Outcomes Registry and Experience.

Author information

1
Queen Elizabeth University Hospital, Glasgow, UK.
2
Azienda Ospedaliera Universitaria Pisana-Ospedale Cisanello-U.O. Malattie Infettive, Pisa, Italy.
3
Departments of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece.
4
Klinik für Herzchirurgie, Universitätsklinik Großhadern, München, Germany.
5
Department of Cardiothoracic Surgery, University of Frankfurt, Frankfurt, Germany.
6
Instituto Cardiovascular de Buenos Aires, Ciudad de Buenos Aires, Argentina.
7
Novartis Healthcare Pvt. Ltd., Hyderabad, India.
8
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. kamal.hamed@novartis.com.

Abstract

INTRODUCTION:

Daptomycin, a rapid concentration-dependent bactericidal antibiotic, is approved at a dose of 4 mg/kg/day for the treatment of complicated skin and soft tissue infections (cSSTI) and at a dose of 6 mg/kg/day for the treatment of Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE. Studies have reported the successful use of high-dose daptomycin (>6 mg/kg/day) in patients with difficult-to-treat infections. The present analysis evaluated the effectiveness and safety of high doses (>6 mg/kg/day) of daptomycin for the treatment of different Gram-positive infections.

METHODS:

European Cubicin(®) Outcomes Registry and Experience (EU-CORE) is a non-interventional, multicenter, retrospective, patient registry designed to collect real-world data from patients treated with daptomycin between 2006 and 2012. Clinical outcomes were assessed at the end of daptomycin treatment for three dose groups: ≤6, >6 to <8, and ≥8 mg/kg/day. Safety was assessed for up to 30 days post-daptomycin treatment.

RESULTS:

Of the 6075 patients enrolled in EU-CORE, 4892 patients received daptomycin doses ≤6 mg/kg/day, while 1097 patients received high doses (>6 mg/kg/day). The primary infections with the largest proportion of patients treated with a high dose (>6 mg/kg/day) were osteomyelitis (37.1%), foreign body/prosthetic infection (31.6%), and endocarditis (27.6%). S. aureus was identified in 42.9% of patients with positive cultures treated with either ≤6 or >6 mg/kg/day. The overall clinical success rate was 82.0% (899/1097) with high doses (>6 mg/kg/day) and 80.3% (3928/4890) with doses ≤6 mg/kg/day. Numerically higher clinical success rate was observed for endocarditis and foreign body/prosthetic infection, as well as for coagulase-negative staphylococcal and enterococcal infections, with high-dose daptomycin treatment. There were no new or unexpected safety findings at doses >6 mg/kg/day.

CONCLUSION:

These results suggested that daptomycin at doses >6 mg/kg/day was effective and well tolerated. High-dose daptomycin is a potential therapeutic option in patients with difficult-to-treat Gram-positive infections.

FUNDING:

This study was funded by Novartis Pharma AG.

KEYWORDS:

Clinical response; Daptomycin; EU-CORE; Gram-positive infections; High dose; Infectious diseases; Safety

PMID:
26610384
PMCID:
PMC4679787
DOI:
10.1007/s12325-015-0267-4
[Indexed for MEDLINE]
Free PMC Article

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