(596) Supratherapeutic Cefepime Trough Concentrations With Label- and Guideline-Directed Dosing in the ICU

Introduction: Cefepime doses are adjusted for renal function and infection type/severity according to prescribing information. Data describing the relationship between dose adjustments and serum trough concentrations in the ICU are lacking. The objective of this study is to determine the proportion of ICU patients who have supratherapeutic cefepime trough concentrations despite receiving an appropriate dose according to FDA prescribing information or applicable clinical practice guidelines.

Methods: This single-center, retrospective cohort study was conducted at an academic medical center between April 2020 and December 2022. Patients were included if they were 18 years of age or older with an ICU admission, received at least one dose of cefepime, and had a trough concentration measured. Patients on renal replacement therapy were excluded. Only the first cefepime trough concentration was evaluated. The cefepime dose at time of trough collection was deemed appropriate if it aligned with FDA prescribing information, or clinical practice guidelines if the indication was not listed in the FDA prescribing information. The reference range for cefepime was 4-38 mg/L since lower concentrations may not achieve pharmacodynamic targets and higher concentrations are associated with neurologic toxicity.

Results: A total of 68 patients were identified and 36 (53%) received an appropriate cefepime dose; median (IQR) age was 62 (54, 69) years, serum creatinine was 0.9 (0.6, 1.9) mg/dL, and estimated creatinine clearance was 100 (77, 142) mL/min. The most common indications for cefepime were pneumonia (18/36; 50%) and central nervous system infections (8/36; 22%). Most of the appropriately dosed patients received 2g q12h (61%), followed by 2g q8h (31%), and 1g q24h (8%). The median cefepime trough concentration was 22.6 (15.5, 51) mg/L. After review, 2 (6%) patients had a trough concentration < 4 mg/L (potentially subtherapeutic), 21 (58%) had a trough concentration 4-38 mg/L (within the reference range), and 13 (36%) had a trough concentration >38 mg/L (neurotoxic).

Conclusions: About a third of ICU patients have a cefepime trough serum concentration outside of the reference range despite appropriate dosing, with the majority having a supratherapeutic concentration. The clinical effect of this requires further study.