Cefepime trough levels and clinical outcomes in patients undergoing universal therapeutic drug monitoring: A prospective cohort study

Abstract

Background: Cefepime is an essential beta-lactam antibiotic for which therapeutic drug monitoring (TDM) is not performed routinely in many centers. Current literature on cefepime levels consists of retrospective reports of TDM applied selectively by clinicians, i.e., in the setting of suspected toxicity. In an effort to capture and define therapeutic plasma concentration thresholds, this prospective study applied TDM uniformly to consecutive inpatients with suspected or confirmed bacterial infections and observed their ensuing 30-day clinical course. Methods: This single-center prospective observational study included adult patients hospitalized in the hematology, intermediate- or intensive-care units of Geneva University Hospitals between January 2019 and December 2021. Participants in steady state (receiving cefepime for ≥24 hours) uniformly underwent TDM at least once and thereafter were assessed for the primary and secondary outcomes of occurrence of adverse events and clinical response, respectively, through 30 days. Results: Among 151 included patients, 104 had at least one trough level. Most (95/104, 91%) experienced clinical success. Six (6%) experienced an adverse event possibly related to cefepime; no neurotoxicity was observed. Median trough level was 8.5 mg/L (IQR 5.8-13.3); trough levels of those with or without adverse events and those with or without clinical success did not differ significantly. Trough levels increased significantly with renal insufficiency and age. Conclusion: Cefepime TDM conducted uniformly in hospitalized patients with severe infections reveals lower trough levels than previously reported. Toxicity is rare and clinical effectiveness is high, such that the determination of a strict therapeutic range remains elusive.

Keywords

• Cefepime
• therapeutic drug monitoring (TDM)
• Adverse events
• Clinical response