621. Pharmacokinetics Determinant and Risk Factors of Daptomycin Induced Eosinophilic Pneumonia and Muscular Toxicity: A Survival Analysis in patients treated for Bone and Joint Infection.

Abstract

Abstract Background Daptomycin prescription for patients suffering from Bone and Joint infections increased in recent years. However, the implication between daptomycin exposure, concomitant factor, and the occurrence of either daptomycin-induced eosinophilic pneumonia (DIEP) or CPK elevation is not clearly understood. Methods All patients treated for a bone and joint infection (BJI) between 2014 and 2021 were screened and classified into cases if they experienced a CPK elevation or DIEP. The controls were randomly selected at a 1:3 ratio within the same period of inclusion. Daptomycin levels were obtained from routine therapeutic drug monitoring. In addition, demographic and biology data were also obtained from the computerized file of patients. Those data were used to compute the area under the concentration-time curve (AUC) of daptomycin using a previously developed population pharmacokinetic model. Finally, a univariate analysis was performed and all data with a p-value < 0.1 were included in the multivariate survival analysis using a proportional Cox hazard model. Results A total of 1130 patients were screened from which 16 patients with DIEP, 42 with CPK elevation, and 107 control were included in the final analysis. Age, CRP, Creatinine, Creatinine Clearance, Serum protein, AUC, and through concentrations were significantly different between case and controls. Summary of univariate analysis is available in table 1. After multivariate analysis, only 3 predictors remained significantly associated with the occurrence of DIEP or CPK elevation. The adjusted hazard ratio of developing DIEP of CPK elevation, were 3.1 (95% CI: 1.48 – 6.5, p < 0.001) for a daptomycin AUC > 939 mg.h/L, 9.8 (95% CI 3.94 – 24.5, p < 0.001) for CRP > 21.6mg/L and 2.4 (95% CI 1.02 – 5.65, p = 0.04] for Protein < 72g/L. Survival curves are shown in figure1. Variable identified in the whole population remained significant in DIEP or CPK subgroup analyses. Table 1.Patients characteristics at time of inclusionFigure 1.Survival analysis of the whole population according to AUC and CRP levels. Conclusion The risk of experiencing DIEP or CPK elevation was greater in patients with an AUC0-24 above 939 mg.h/L and a CRP > 21.6mg/L. Daptomycin Therapeutic drug monitoring should be performed and an AUC range of 666 to 939 mg.h/L should be targeted in order to maximize efficacy and minimize the risk of adverse events, especially for patients with an inflammatory syndrome. Disclosures All Authors: No reported disclosures.