Cefepime exposure in prolonged or intermittent infusion in critically ill children.

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.