Pharmacokinetic Analysis of Intravenous Push Cefepime in Critically Ill Patients With Sepsis

Intravenous push (IVP) administration of cefepime increases ease of preparation and limits the need for small volume parenterals. The data on IVP pharmacokinetic/pharmacodynamic (PK/PD) parameters are limited, but may be especially relevant in critically ill patients with altered PK/PD for time-dependent antibiotics like cefepime. The objective of this study was to characterize the PK profile and PD target attainment of IVP cefepime in critically ill patients with sepsis.

In this institutional review board-approved, prospective, noninterventional PK study, hospitalized adult patients receiving IVP cefepime were included if they had a central/midline catheter, intensive care unit (ICU) length of stay ≥ 48 h, creatinine clearance > 30 mL/min without renal replacement therapy, and diagnosis of sepsis. Blood samples were obtained at cefepime steady state immediately before and at 5, 15, 30, 60, 120, and 240 min after a dose. Serum concentrations of cefepime were measured using high-performance liquid chromatography with ultraviolet detection. Patient characteristics and outcomes were collected retrospectively from the electronic health record. The primary outcome was the PK profile of cefepime following IVP administration.

Patients (n = 17) had a median age of 69 years, body mass index (BMI) of 29.9 kg/m², creatinine clearance of 94 mL/min, and sequential organ failure assessment (SOFA) score of 9. Following IVP administration, PK analysis demonstrated a maximum concentration (C_max) of 158 μg/mL, time to maximum concentration (T_max) of 5 min, area under the curve (AUC) of 286.95 μg × h/mL, and elimination rate constant (K_e) of 0.31 h^-1. Additionally, the analysis showed a volume of distribution of 43.91 L, elimination half-life (t_½) of 3.76 h, clearance (CL) of 7.86 L/h, and time above minimum inhibitory concentration (T > MIC) of 86%.

Intravenous push cefepime in critically ill patients achieved systemic exposure comparable to traditional intermittent infusion but demonstrated substantial interpatient PK variability. These findings highlight the impact of critical illness on cefepime disposition and support further evaluation of personalized cefepime dosing for the ICU population.