Advances in Pediatric Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is indicated for drugs with narrow therapeutic indices, whereby clinicians can adjust drug dosing to promote efficacy while limiting toxicity risk. Such monitoring is particularly important in managing infectious diseases, as both patient- and organism-specific factors must be considered to achieve optimal clinical responses. Innovation in pediatric TDM lags behind adults, largely due to a paucity of data and feasibility issues with lab draws and pharmacy resources. Emerging techniques in pharmacokinetic (PK) modeling, PK study design, flexible sampling strategies, and reduced sample volume requirements are particularly promising for TDM advancement in neonates and children. In this article, we discuss recent advancements in vancomycin TDM as a model case. Vancomycin is commonly used to treat serious gram-positive infections in children, and monitoring was historically performed using trough concentration-based guidance. Emerging data suggest that vancomycin troughs are not reliable surrogates for efficacy or toxicity and that trough-based monitoring is associated with increased risk of nephrotoxicity without clinical benefits. The area under the concentration-time curve (AUC) is the optimal pharmacokinetic-pharmacodynamic metric to measure overall vancomycin exposures, and consensus infectious diseases and pharmacist society guidance has formally recommended a shift toward AUC-based monitoring and away from trough-based monitoring in all age groups-including in neonates and children. We compare approaches to TDM in infectious diseases and summarize the body of literature describing application of vancomycin AUC-guided monitoring in children and neonates. Finally, we highlight opportunities and potential barriers to implementation of AUC-guided TDM in pediatric populations.