Dosing strategy to allow continued therapy with daptomycin after asymptomatic increases in creatine kinase levels.

Abstract

A case series in which a novel dosing strategy for managing mild, asymptomatic creatine kinase (CK) increases associated with daptomycin therapy is presented. Eight patients received a mean daptomycin dosage of 7.75 mg/kg/day for a median duration of 42 days. Seven of the eight patients were being treated for a bone and joint infection, and all but one had methicillin-resistant Staphylococcus aureus. All patients had asymptomatic increases in CK concentrations during daptomycin therapy (peak range, 400-1200 IU/L). A single daptomycin dose was withheld from each patient, and therapy was resumed 24 hours later, most often at the same dosage. The elevated CK values in these patients resolved, and all patients were able to complete daptomycin therapy without further increases in CK elevations. These findings indicate that withholding one dose of daptomycin during treatment may allow patients with asymptomatic, elevated CK concentrations to continue therapy with CK level normalization. Although the mechanism of daptomycin-mediated muscle injury is not fully understood, a reduction in daptomycin exposure via a one-dose cessation of therapy may allow for physiological restoration of sarcolemma membrane integrity that may be disrupted by daptomycin in individuals exhibiting CK elevation. A single daptomycin dose was withheld from eight patients with asymptomatic increases in serum CK concentrations, then daptomycin therapy was resumed 24 hours later, most often at the previous dosage. The CK concentrations returned to normal, and all patients were able to complete daptomycin therapy without further increases in CK concentrations.