Observational studyThe Journal of antimicrobial chemotherapy2026
Real-world validation of a reduced-dose continuous infusion cefepime regimen: pharmacodynamic target attainment, efficacy and neurotoxicity.
Observational study in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCefepime 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.
methodsWe 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.
resultsAmong 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.
conclusionA 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.
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