Characterization of skeletal muscle effects associated with daptomycin in rats.
Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram-positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (<or=0.22%) with loss of plasma membrane integrity and/or infiltration by neutrophils and/or macrophages. Multiple doses of daptomycin are required for a quantifiable effect on skeletal muscles of rats. Some fibers were Evans Blue Dye-positive but were not yet infiltrated by neutrophils. This suggests that the sarcolemma may be the primary target for the observed effects.
Kostrominova
Tatiana Y
TY
Department of Molecular and Integrative Physiology, BSRB, University of Michigan, Ann Arbor, Michigan, USA. tkostrom@iun.edu
Hassett
Cheryl A
CA
Rader
Erik P
EP
Davis
Carol
C
Larkin
Lisa M
LM
Coleman
Scott
S
Oleson
Frederick B
FB
Faulkner
John A
JA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D017576:Daptomycin / Q000008:administration & dosage / Q000633:toxicity*; D005070:Evans Blue; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005070:Evans Blue; D017576:Daptomycin