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Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds

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High-dose daptomycin in documented Staphylococcus aureus infections.

Matteo Bassetti¹, Elena Nicco, Francesca Ginocchio

¹Infectious Diseases Division, San Martino Hospital and University of Genoa School of Medicine, Genoa, Italy. matteo.bassetti@hsanmartino.it

International Journal of Antimicrobial Agents

|September 18, 2010

Summary

Higher doses of daptomycin (mean 8 mg/kg/day) showed improved clinical and microbiological success for Staphylococcus aureus infections compared to standard doses (mean 5 mg/kg/day), with similar safety profiles.

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Area of Science:

Infectious Diseases
Pharmacology
Clinical Microbiology

Background:

Daptomycin is FDA-approved for complicated skin and soft-tissue infections and Staphylococcus aureus bloodstream infections at 4-6 mg/kg/day.
Limited data exist on daptomycin use at doses exceeding 6 mg/kg/day, though some suggest potential safety and efficacy.

Purpose of the Study:

To evaluate the safety and efficacy of higher-dose daptomycin (HD) compared to standard-dose daptomycin (SD) in patients with Staphylococcus aureus infections.

Main Methods:

Retrospective chart review of 53 patients treated with daptomycin from January 2008 to February 2010.
Patients were divided into SD (4-6 mg/kg/day) and HD (7-9 mg/kg/day) groups.
Clinical and microbiological success rates, as well as adverse events, were compared between groups.

Main Results:

Clinical success was higher in the HD group (94%) compared to the SD group (73%) (P=0.05).
Microbiological success was significantly higher in the HD group (93%) versus the SD group (68%) (P<0.05).
Adverse events were minimal and comparable between groups, with no treatment discontinuations.

Conclusions:

Daptomycin doses higher than 6 mg/kg/day appear safe and potentially more effective than standard doses for Staphylococcus aureus infections.
Further randomized controlled trials are recommended to confirm the efficacy of higher daptomycin doses.