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Characterization of skeletal muscle effects associated with daptomycin in rats

Tatiana Y Kostrominova1, Cheryl A Hassett, Erik P Rader

  • 1Department of Molecular and Integrative Physiology, BSRB, University of Michigan, Ann Arbor, Michigan, USA. tkostrom@iun.edu

Muscle & Nerve
|June 15, 2010
PubMed

Insights

Multiple doses of daptomycin are needed to affect rat skeletal muscles. Early effects include plasma membrane damage in a small percentage of muscle fibers, suggesting the sarcolemma is the primary target.

Area of Science:

  • Pharmacology
  • Toxicology
  • Muscle Physiology

Background:

  • Daptomycin is a lipopeptide antibiotic effective against Gram-positive bacteria.
  • Skeletal muscle side effects are generally considered minor.

Purpose of the Study:

  • To investigate the early effects and dose-dependency of daptomycin on rat skeletal muscle.
  • To identify the primary cellular targets of daptomycin-induced muscle toxicity.

Main Methods:

  • Histopathology and neutrophil/macrophage infiltration assessment.
  • Measurement of muscle contractile properties.
  • Evans Blue Dye uptake to evaluate sarcolemmal integrity.
  • Evaluation of muscle patch repair processes.

Main Results:

  • A single dose of daptomycin up to 200 mg/kg showed no effect on muscle fibers.
  • Repeated administration (150 mg/kg twice daily for 3 days) resulted in <0.22% myofibers with plasma membrane damage.
  • Evans Blue Dye uptake preceded neutrophil infiltration, indicating early sarcolemmal damage.

Conclusions:

  • Quantifiable skeletal muscle effects from daptomycin require multiple doses in rats.
  • The sarcolemma appears to be the initial site of daptomycin-induced muscle injury.

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