Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of ß-Lactam Antibiotics in Critically Ill Children.

There has been increasing interest in incorporating ß-lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration-versus-time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach. A prospective observational study was conducted in a single-center pediatric intensive care unit, where pediatric patients administered at least 1 dose of cefepime, meropenem, or piperacillin/tazobactam and who had residual blood scavenged from samples obtained for routine clinical care were enrolled. A total of 138 samples from 22 pediatric patients were collected in a 2-week period. For all 3 antibiotics, the samples collected covered the entire dosing intervals and were not clustered around specific times. There was high variability in the free concentrations and in the percentage of drug bound to protein. There was less than 15% degradation for meropenem or piperacillin when stored in whole blood or plasma at 4°C after 6 days. Cefepime degraded by more than 15% after 3 days. The opportunistic sampling approach is a powerful and feasible method to obtain sufficient samples to study the variability of drug concentrations and protein binding for future pharmacokinetic studies in the pediatric critical care population.

Route of Oseltamivir Administration Affects Metabolite Concentrations in Critically Ill Children.

We performed a prospective cohort study to investigate oseltamivir administration in critically ill children. We found that enteric tube administration of oseltamivir resulted in lower concentrations of its active metabolite compared with oral delivery. These findings could have significant clinical implications, and more studies are required to better understand the effects of administration route on potential lower systemic metabolite exposure.