Real-world validation of a reduced-dose continuous infusion cefepime regimen: pharmacodynamic target attainment, efficacy and neurotoxicity.

BACKGROUND

Cefepime is a key carbapenem-sparing agent due to its stability against AmpC β-lactamases. However, high plasma concentrations are associated with cefepime-induced neurotoxicity (CIN). Following 2019 EUCAST reclassification of 'intermediate' as 'susceptible, increased exposure', higher doses (6 g/day) are often recommended. Pharmacokinetic/pharmacodynamic (PK/PD) simulations suggest that a reduced daily dose of cefepime 4 g/day administered by continuous infusion may achieve adequate target attainment while limiting toxicity, but real-world clinical data are scarce.

METHODS

We conducted a prospective, single-centre observational study including adult inpatients treated with cefepime administered as a 2 g loading dose followed by continuous infusion of 4 g/day. Therapeutic drug monitoring was performed to assess steady-state free cefepime concentrations (ƒCss). The primary endpoint was pharmacodynamic target attainment (100% ƒT > MIC) for EUCAST 'susceptible, increased exposure' breakpoints.

RESULTS

Among 46 included patients, median ƒCss was 26.2 mg/L (IQR 18.4-33.2). Pharmacodynamic targets were achieved in 96% of patients for Enterobacterales (MIC 4 mg/L) and 93% for Pseudomonas aeruginosa (MIC 8 mg/L). Clinical efficacy was observed in 96% of cases. Signs consistent with CIN occurred in three patients (6.5%), mainly in the context of renal function deterioration or pre-existing neurological vulnerability.

CONCLUSION

A reduced-dose cefepime regimen consisting of 4 g/day administered by continuous infusion achieves high pharmacodynamic target attainment with a favourable efficacy-toxicity balance in real-life clinical practice. This strategy represents a promising alternative to higher-dose regimens and supports individualized dosing guided by renal function and therapeutic drug monitoring.