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Safety and clinical outcomes when utilizing high-dose (> or =8 mg/kg) daptomycin therapy

Pamela A Moise1, Ellie Hershberger, Maria I Amodio-Groton

  • 1Cubist Pharmaceuticals Inc., Lexington, MA 02421, USA. pamela.moise@cubist.com

The Annals of Pharmacotherapy
|July 9, 2009
PubMed
Abstract

Insights

Higher doses of daptomycin (≥8 mg/kg) demonstrated good tolerability and effectiveness in treating gram-positive infections. These findings support further investigation into higher daptomycin dosing for complex infections.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Clinical Medicine

Background:

  • Daptomycin is FDA-approved for skin infections (4 mg/kg) and Staphylococcus aureus bacteremia (6 mg/kg).
  • Limited clinical data exist for daptomycin doses exceeding 6 mg/kg.
  • In vitro and animal studies suggest enhanced daptomycin activity at higher doses.

Purpose of the Study:

  • To assess the safety and efficacy of higher daptomycin doses (≥8 mg/kg).
  • To evaluate daptomycin's utility in treating various gram-positive bacterial infections.

Main Methods:

  • Retrospective data analysis from the Cubicin Outcomes Registry and Experience database (2005-2007).
  • Inclusion criteria: patients receiving daptomycin at ≥8 mg/kg.
  • Evaluation of safety and efficacy in this patient cohort.

Main Results:

  • Ninety-four patients received daptomycin ≥8 mg/kg; 18 received ≥10 mg/kg.
  • Common infections included bacteremia (30/94), skin infections (22/94), and endocarditis (15/94).
  • Pathogens included vancomycin-resistant Enterococcus spp. (57%) and methicillin-resistant S. aureus (68%).
  • Adverse events possibly related to daptomycin occurred in 6.4% of patients, with discontinuation in 2.1%.
  • Clinical success rate was 89% in evaluable patients (79%).

Conclusions:

  • Daptomycin at doses of 8 mg/kg or higher is well-tolerated and effective for gram-positive infections.
  • Higher daptomycin doses show promise, particularly for challenging infections.
  • Prospective, comparative studies of daptomycin >6 mg/kg are warranted.

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