Neonates are not just little children and need more finesse in dosing of antibiotics

Abstract

Objectives: Neonates are not just little children. They need more finesse in decisions on when to treat, which antibiotics to use and how to dose these antibiotics.

Methods: Representative compounds of three major classes of antibiotics (beta-lactams, aminoglycosides, glycopeptides) are discussed in a narrative review to illustrate the recent progress in the knowledge on PK and its covariates (how to dose).

Results: This knowledge can subsequently be converted to targeted exposure dosing regimens. This is because it is reasonable to postulate that pharmacodynamics (PD) of antibiotics are similar in neonates to that in other populations if a similar concentration–time profile and targeted exposure are attained. However, this approach has its limitations, since the clinical response may be different in neonates because of maturational differences in innate immunity or toxicity. These dosing regimens should at least be validated.

Conclusion:Relevant information on the PK of antibiotics and its covariates have been generated, but the next steps are to validate the dosing regimens suggested, and consider more sophisticated dosing regimens. This approach should subsequently pave the way to conduct comparative studies to assess the efficacy and safety of these commonly used drugs in neonates.

Keywords:

• Pharmacokinetics
• pharmacodynamics
• newborn
• antibiotics
• PK-PD studies
• clinical pharmacology

Acknowledgments

The clinical research activities of Karel Allegaert were facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033).