Cefepime Concentration-Toxicity Relationship in Hematological Patients Treated With Continuous Infusion: A...

Area of Science:

• Pharmacology
• Neuroscience
• Hematology

Background:

• Cefepime-induced neurotoxicity (CIN) is a recognized complication, but a clear threshold for toxic drug concentrations is lacking.
• Understanding this threshold is crucial for safe cefepime administration, especially in vulnerable patient populations.

Purpose of the Study:

• To investigate the association between cefepime plasma exposure and the incidence of neurotoxicity.
• To establish a specific cefepime steady-state concentration (Css) threshold indicative of neurotoxicity.
• To identify factors influencing cefepime-induced neurotoxicity.

Main Methods:

• Prospective, single-center study involving patients with febrile neutropenia receiving continuous infusion cefepime.
• Regular monitoring of cefepime steady-state concentrations (Css) and neurological assessments over the first 10 days.
• Multivariable analysis and ROC curve analysis to determine the relationship between Css and neurotoxicity, and to identify a predictive threshold.

Main Results:

• Cefepime-induced neurotoxicity (CIN) occurred in 9.7% of treatment courses.
• Both increased cefepime Css and concomitant chimeric antigen receptor T-cell therapy were independently associated with CIN.
• A cefepime Css threshold of 36.7 mg/L demonstrated high sensitivity (89%) and specificity (90%) for predicting neurotoxicity.

Conclusions:

• Cefepime exposure is a significant risk factor for neurotoxicity, independent of other factors like CAR T-cell therapy.
• The identified threshold of 36.7 mg/L provides a practical tool for managing high-dose cefepime therapy and preventing neurotoxicity.
• This study offers valuable real-world data for optimizing cefepime dosing strategies in clinical practice.