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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 normal 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 normal 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 the total risk scores of ≤4, 5–6, and ≥8, respectively. The risk prediction model exhibited a good fit (area under the receiving-operating characteristic curve 0.85, 95% CI 0.74–0.95). 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.

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The present systematic review and meta-analysis evaluated the incidence of elevated creatine phosphokinase (CPK) levels between daptomycin alone and concomitant daptomycin and statin use. Methods:We searched the PubMed, Web of Sciences, Cochrane Library and ClinicalTrials.gov databases. We analysed the incidence of elevated CPK between daptomycin alone and concomitant daptomycin and statins among studies defining CPK elevation as levels ≥ the upper limit of normal (ULN) or ≥5Â ULN. We also analysed the incidence of rhabdomyolysis between the groups. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) based on the included studies.Results: Comparing CPK elevation defined as CPK levels ≥ULN, a significantly higher incidence of CPK elevation was observed with concomitant daptomycin and statin use than with daptomycin alone (OR = 2.55, 95% CI 1.78-3.64, P < .00001, I 2 = 0%).Likewise, when CPK elevation was defined as CPK levels ≥5Â ULN, a significantly higher incidence of CPK elevation was detected with concomitant daptomycin and statin use than with daptomycin alone (OR = 1.89, 95% CI 1.06-3.35, P = .03, I 2 = 48%). The incidence of rhabdomyolysis was significantly higher following concomitant daptomycin and statin use than with daptomycin alone (OR = 11.60, 95% CI 1.81-74.37, P = .01, I 2 = 0%). Conclusion:The combined use of daptomycin and statins were significant risk factors for the incidence of CPK elevation defined as levels ≥ULN or ≥5Â ULN and rhabdomyolysis.

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