Cefepime exposure in prolonged or intermittent infusion in critically ill children

Cefepime is commonly used in critically ill children for whom there is a high between-subject variability. To reach the therapeutic pharmacokinetic (PK) target in critically ill patients, prolonged infusion of beta-lactams seems to be the most efficient. The aim of this study was to compare cefepime exposure between prolonged and intermittent infusions in critically ill children.

This prospective observational study was conducted in two paediatric intensive care units. Children with a cefepime plasma concentration measurement were included. Steady-state free residual and plateau concentrations were estimated using Bayesian forecasting. The PK target was defined as 100% fT_≥4xMIC. Exposure was compared using the minimum inhibitory concentrations (MICs) of the pathogens identified in the patients. The probability of target attainment (PTA) was also compared using various MICs.

Seventy-eight antibiotic courses in 75 patients were included, divided into 19 prolonged infusions and 59 intermittent infusions. Prolonged and intermittent infusions were comparable for optimal exposure (n = 10/19, 53% vs. n = 35/59, 59%, p = .79). Overexposure tended to be more frequent with prolonged infusion (n = 8/19, 42% vs. n = 16/59, 27%, p = .26), whereas underexposure tended to be less common with prolonged infusion (n = 1/19, 5% vs. n = 8/59, 14%, p = .44). Considering the wide range of MICs, the PTA was comparable for MIC < 1 mg/L but was significantly higher for prolonged infusion for MIC ≥ 1 mg/L (p < .05).

Prolonged infusion of cefepime provides a higher PTA when MIC is ≥1 mg/L compared with intermittent infusion. This result suggests the superiority of prolonged infusion for high MIC bacteria.