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Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis.
Clin Infect Dis. 2010 Jun 15; 50(12):1568-74.CI

Abstract

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 (C(min)) 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. C(min) (breakpoint of 24.3 mg/L) was most significantly associated with CPK elevation (P = .002). The probabilities of a CPK elevation with a C(min) 24.3 mg/L and <24.3 mg/L were 0.5 and 0.029, respectively. Increases in C(min), evaluated as a continuous variable, were also significantly associated with CPK elevation (P = .01). Stratified Kaplan-Meier analysis and Cox proportional hazards regression demonstrated C(min) to be a significant predictor of time to a CPK elevation (P .003). The probability of a CPK elevation was 0 and 0.01 after 7 days of treatment in patients with a C(min) 24.3 mg/L or <24.3 mg/L, respectively. After 14 days, the probabilities were 0.5 and 0.025, respectively.

CONCLUSIONS

This analysis demonstrated that a daptomycin C(min) 24.3 mg/L was associated with an increased probability of a CPK elevation. Clinical trials registration. Clinical trials.gov NCT00093067 .

Authors+Show Affiliations

Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20462352

Citation

Bhavnani, Sujata M., et al. "Daptomycin Exposure and the Probability of Elevations in the Creatine Phosphokinase Level: Data From a Randomized Trial of Patients With Bacteremia and Endocarditis." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 50, no. 12, 2010, pp. 1568-74.
Bhavnani SM, Rubino CM, Ambrose PG, et al. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis. 2010;50(12):1568-74.
Bhavnani, S. M., Rubino, C. M., Ambrose, P. G., & Drusano, G. L. (2010). Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 50(12), 1568-74. https://doi.org/10.1086/652767
Bhavnani SM, et al. Daptomycin Exposure and the Probability of Elevations in the Creatine Phosphokinase Level: Data From a Randomized Trial of Patients With Bacteremia and Endocarditis. Clin Infect Dis. 2010 Jun 15;50(12):1568-74. PubMed PMID: 20462352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. AU - Bhavnani,Sujata M, AU - Rubino,Christopher M, AU - Ambrose,Paul G, AU - Drusano,George L, PY - 2010/5/14/entrez PY - 2010/5/14/pubmed PY - 2010/7/28/medline SP - 1568 EP - 74 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 50 IS - 12 N2 - 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 (C(min)) 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. C(min) (breakpoint of 24.3 mg/L) was most significantly associated with CPK elevation (P = .002). The probabilities of a CPK elevation with a C(min) 24.3 mg/L and <24.3 mg/L were 0.5 and 0.029, respectively. Increases in C(min), evaluated as a continuous variable, were also significantly associated with CPK elevation (P = .01). Stratified Kaplan-Meier analysis and Cox proportional hazards regression demonstrated C(min) to be a significant predictor of time to a CPK elevation (P .003). The probability of a CPK elevation was 0 and 0.01 after 7 days of treatment in patients with a C(min) 24.3 mg/L or <24.3 mg/L, respectively. After 14 days, the probabilities were 0.5 and 0.025, respectively. CONCLUSIONS: This analysis demonstrated that a daptomycin C(min) 24.3 mg/L was associated with an increased probability of a CPK elevation. Clinical trials registration. Clinical trials.gov NCT00093067 . SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/20462352/Daptomycin_exposure_and_the_probability_of_elevations_in_the_creatine_phosphokinase_level:_data_from_a_randomized_trial_of_patients_with_bacteremia_and_endocarditis_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1086/652767 DB - PRIME DP - Unbound Medicine ER -