Pharmacokinetic and pharmacodynamic considerations of cephalosporin use in children

Abstract

Introduction: Cephalosporins are a major class of antibiotics, frequently used in children because of their remarkable antibacterial activity and excellent safety profile. Time above the minimal inhibitory concentration of the non-protein-bound fraction (fT>MIC) is the pharmacokinetic/pharmacodynamic parameter that correlates with the therapeutic efficacy. In the pediatric population, the inter-individual variability in cephalosporin pharmacokinetics is large because of maturational changes. However, the prescription of cephalosporins promotes emergence of Enterobacteriaceae producing broad-spectrum ß-lactamases.Areas covered: Here we describe in vitro activities and the main pharmacokinetic characteristics of cephalosporins in children. On the basis of these characteristics, we propose an estimation of the fT>MIC for each molecule as a tool to help optimize the use of cephalosporins. We also provide an inventory of the clinical use of cephalosporins and present prospects for the development of new molecules or associations to address the emergence of resistant strains.Expert opinion: Cephalosporins represent a heterogeneous group of antibiotics with various pharmacokinetics and in vitro antimicrobial activity that the clinician needs to master to optimize their use. However, their broad use plays a role in the emergence of broad-spectrum ß-lactamase-producing strains and must thus be restricted to probabilistic broad-spectrum therapy and situations without therapeutic alternatives.

Keywords: Cephalosporins; children; extended spectrum ß-lactamases; neonates; pharmacodynamics; pharmacokinetics.