Antibiotic Dosing in Pediatric Critically Ill Patients

Despite being some of the most frequently utilized drugs in children, caregivers still commonly prescribe antibiotics in neonates and children based on dosing regimens linearly extrapolated from adults. Although this practice is not limited to antibiotics, specific concerns related to dosing inaccuracy for antibiotics are treatment failure, antimicrobial resistance, and maturational toxicity. In this chapter, we first discuss the simultaneous impact of maturation and critical illness on pediatric pharmacokinetics (PK), including the specific impact of major burns and extracorporeal equipment. Both aspects (maturation and critical illness) will play a significant role in the final, phenotypic PK in a given child. Second, a section on pharmacodynamics (PD) focuses on the developmental safety of antibiotics. Developmental PD aspects may result in differences in risk rate, or altogether different risks compared to adult observations. Third, some compound-specific PK/PD observations (aminoglycosides, vancomycin, meropenem) in neonates and children are discussed to further illustrate the complex interaction between physiology and pathophysiology, including the limitations of the currently available guidance. In the final part of the chapter, the contribution of PK modeling and simulation and advanced therapeutic drug monitoring is explored as a tool towards tailored pharmacotherapy in pediatric critically ill patients.