Cefepime pharmacokinetics in critically ill children with multiple organ dysfunction syndrome using volumetric absorptive microsampling

Up to half of critically ill children experience multiple organ dysfunction syndrome (MODS), which worsens outcomes and increases mortality risk. Cefepime is a broad-spectrum antibiotic commonly used in pediatric sepsis, but its pharmacokinetics during MODS has not been evaluated. We performed a prospective, observational study of critically ill children with MODS who were administered cefepime and collected up to 15 whole blood samples over 3 days using volumetric absorptive microsampling (VAMS). We performed nonlinear mixed-effects modeling to develop a population PK model for cefepime in children with MODS. We then reran our final population PK model using estimated plasma concentrations based on a 0.58:1 VAMS:plasma ratio derived ex vivo. A two-compartment model with allometric scaling best described the data. Estimated glomerular filtration rate and age were significant covariates on total body clearance and central volume, respectively. Final model parameter estimates for clearance and central volume in VAMS were 5.14 L/h and 20.5 L, respectively, for a 36-kg child. Estimates for clearance and central volume in plasma were 2.97 L/h and 11.51 L, respectively. We provide the first population PK model of cefepime in critically ill children with MODS based on VAMS, along with estimated plasma PK derived from VAMS data. Our study demonstrates the feasibility of using a novel microsampling approach to evaluate antimicrobial PK in critically ill children and provides the groundwork to better understand how this approach can optimize treatment and monitoring in this population.