Pharmacodynamic Considerations and Special Populations: Pediatrics

Abstract

The complexity of infectious disease pharmacotherapy intensifies in pediatric patients since two pertinent elements must be accounted for—the immunologic and physiologic developmental processes that occur with age. Physiologic development may alter the pharmacokinetics of a drug with enhanced clearance to potentially result in subtherapeutic responses, while overexposure may have consequences for adverse events, especially in young, rapidly growing neonates and infants. Understanding the pharmacokinetic variability stemming from age-related physiologic maturation and the pharmacodynamic target effect (or desired response) can assist the clinician in selecting the ideal antimicrobial agent and dosing regimen. This chapter presents the following: (1) the factors (including physiologic maturation, organ function, and size) that contribute to pharmacokinetic alterations that occur with age; (2) the impact of immunologic development on microbiologic and clinical outcomes; (3) the unique exposure-response relationship, or the pharmacodynamic index for antimicrobial agents in pediatrics; (4) critical review of specific antibacterial agents with recent information in the literature (including beta-lactams, aminoglycosides, and vancomy-cin); and (5) overcoming challenges to pharmacokinetic-pharmacodynamic studies in pediatrics.