(521) Cefepime Therapeutic Drug Monitoring in ICU Patients Receiving Continuous Venovenous Hemodialysis

Introduction: There is limited and variable literature describing the optimal dosing of cefepime in continuous veno-venous hemodialysis (CVVHD). The goal of this study is to describe cefepime pharmacokinetics (PK) as well as investigate the factors that predict the achievement of PK/pharmacodynamic (PD) targets, attainment of supratherapeutic cefepime levels, and occurrence of potential cefepime-induced neurotoxicity (CIN) in critically ill patients receiving CVVHD.

Methods: This was a single-center, retrospective, observational study of adult patients admitted to the intensive care unit between June 2019 and March 2023 who received cefepime therapeutic drug monitoring (TDM) while on CVVHD. The primary efficacy outcome was the achievement of target total plasma cefepime concentration ≥ 4 times the minimum inhibitory concentration (MIC) (fT ≥ 4 x MIC) for the pathogen for 100% of the dosing interval. Assuming a cefepime-susceptible Pseudomonas aeruginosa with an MIC of 8, efficacy was defined as a trough cefepime total plasma concentration ≥ 32 mcg/mL. Safety outcomes include supratherapeutic cefepime level (trough ≥ 64 mcg/mL) and potential CIN. Binomial logistic regressions were performed to assess the association between clinical and PK factors, and the achievement of efficacy and safety endpoints. The presence of potential CIN was assessed using the Naranjo scale and a binomial logistic regression was performed to identify risk factors for its development.

Results: Out of 65 patients screened, 45 patients were included. Efficacy was achieved in 62.2% of patients, with cefepime total daily dose (TDD) > 3 g associated with an increased likelihood of achieving a cefepime trough ≥ 32 mcg/mL (p=0.043). The safety endpoint occurred in 33.33% of patients, with higher BMI (p=0.049), cefepime TDD > 3 g (p=0.029), and lower CVVHD therapy fluid rates (p=0.033) associated with an increased likelihood of attaining a cefepime trough ≥ 64 mcg/mL. Potential CIN occurred in 28.8% of patients, with higher cefepime trough levels associated with an increased likelihood of developing CIN (p=0.033).

Conclusions: Efficacy and safety of cefepime are influenced by cefepime TDD and CVVHD therapy fluid rate. Given the risk of potential CIN, cefepime dosing should be guided based on TDM in critically ill patients requiring CVVHD.