Identification of Risk Factors for Daptomycin-Associated Creatine Phosphokinase Elevation and Development of a Risk Prediction Model for Incidence Probability

Background: In this study, we investigated the risk factors for daptomycin-associated creatine phosphokinase (CPK) elevation and established a risk score for CPK elevation. Methods: Patients who received daptomycin at our hospital were classified into the non-elevated or elevated CPK group based on their peak CPK levels during daptomycin therapy. Univariable and multivariable analyses were performed, and a risk score and prediction model for the incidence probability of CPK elevation were calculated based on logistic regression analysis. Results: The non-elevated and elevated CPK groups included 181 and 17 patients, respectively. Logistic regression analysis revealed that concomitant statin use (odds ratio [OR], 4.45 [95% confidence interval {CI}, 1.40-14.47]; risk score 4), concomitant antihistamine use (OR, 5.66 [95% CI, 1.58-20.75]; risk score 4), and trough concentration (Cmin) between 20 and <30 μg/mL (OR, 14.48 [95% CI, 2.90-87.13]; risk score 5) and ≥30.0 μg/mL (OR, 24.64 [95% CI, 3.21-204.53]; risk score 5) were risk factors for daptomycin-associated CPK elevation. The predicted incidence probabilities of CPK elevation were <10% (low risk), 10%-<25% (moderate risk), and ≥25% (high risk) with total risk scores of ≤4, 5-6, and ≥8, respectively. The risk prediction model exhibited a good fit (area under the receiver operating characteristic curve, 0.85 [95% CI,. 74-.95]). Conclusions: These results suggested that concomitant use of statins with antihistamines and Cmin ≥20 μg/mL were risk factors for daptomycin-associated CPK elevation. Our prediction model might aid in reducing the incidence of daptomycin-associated CPK elevation.