Daptomycin Exposure and the Probability of Elevations in the Creatine Phosphokinase Level: Data from a Randomized Trial of Patients with Bacteremia and Endocarditis

• Published in: Clinical infectious diseases 2010-06, Vol.50 (12), p.1568-1574
• Main Authors: Bhavnani, Sujata M., Rubino, Christopher M., Ambrose, Paul G., Drusano, George L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; ARTICLES AND COMMENTARIES; Bacteremia; Bacteremia - blood; Bacteremia - drug therapy; Bacterial diseases; Bacterial infections; Bacterial sepsis; Biological and medical sciences; Body weight; Cardiology. Vascular system; Cardiovascular disease; Clinical trials; Creatine; Creatine Kinase - blood; Daptomycin - adverse effects; Daptomycin - therapeutic use; Dosage; Drug design; Drug therapy; Endocardial and cardiac valvular diseases; Endocarditis; Endocarditis, Bacterial - blood; Endocarditis, Bacterial - drug therapy; Heart; Human bacterial diseases; Humans; Infections; Infectious diseases; Medical sciences; Middle Aged; Obesity; Pharmacokinetics; Pharmacology. Drug treatments; Probability; Staphylococcal Infections - blood; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus infections
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/652767

Background. The objective of this analysis was to evaluate the relationship between daptomycin exposure and the probability of an elevation in the creatine phosphokinase (CPK) level (hereafter, “CPK elevation”) in patients with Staphylococcus aureus bacteremia with or without infective endocarditis. Methods. Phase 3 data for patients with S. aureus bacteremia, with or without infective endocarditis, who received intravenous daptomycin (6 mg/kg daily) and in whom pharmacokinetic data were collected were evaluated. On the basis of univariate logistic regression, the relationship between Bayesian post hoc exposure estimates and the probability of a CPK elevation was evaluated. Time to CPK elevation was examined with Kaplan-Meier analysis and Cox proportional hazards regression. Results. Significant relationships between the minimum concentration of drug (Cmin) and area under the plasma concentration time curve and probability of CPK elevation were observed in 108 evaluable patients. Of the 108 patients evaluated, 6 (5.56%) demonstrated a defined CPK elevation, regardless of treatment relationship. Cmin (breakpoint of 24.3 mg/L) was most significantly associated with CPK elevation (P = .002). The probabilities of a CPK elevation with a Cmin ⩾24.3 mg/L and