Factors affecting creatine phosphokinase elevation during daptomycin therapy using a combination of machine learning...

Area of Science:

• Pharmacology
• Toxicology
• Data Science

Background:

• Musculoskeletal toxicity is a common side effect of daptomycin (DAP).
• Risk factors for DAP-induced musculoskeletal toxicity remain incompletely understood.
• Identifying these factors is crucial for patient safety and effective treatment.

Purpose of the Study:

• To identify independent risk factors for daptomycin-induced musculoskeletal toxicity.
• To utilize a combination of machine learning and conventional statistical methods for risk factor identification.
• To improve the prediction and management of DAP-related adverse events.

Main Methods:

• A retrospective, population-based cohort study using Japanese electronic medical records (October 2011 - December 2020).
• Inclusion of patients receiving daptomycin, with analysis of creatine phosphokinase (CPK) elevation (>200 IU/L and >1000 IU/L).
• Application of multiple logistic regression and decision tree analyses to identify risk factors and their combinations.

Main Results:

• Of 2970 patients, 706 were analyzed. CPK elevations (>200 IU/L and >1000 IU/L) occurred in 11.8% and 2.41% respectively.
• Multiple logistic regression identified baseline CPK and concomitant hydrophobic statin use as independent risk factors.
• Decision tree analysis highlighted patients with high baseline CPK and hydrophobic statin use as a high-risk group.

Conclusions:

• This study identified novel risk factors for daptomycin-induced CPK elevation.
• Concomitant use of hydrophobic statins and elevated baseline CPK are significant risk factors.
• High-risk patients identified by these factors warrant frequent CPK monitoring to prevent severe musculoskeletal toxicity.