Karel Allegaert1,2,3, John van den Anker1,4,5. 1. a Intensive Care and Department of Pediatric Surgery , Erasmus MC - Sophia Children's Hospital , Rotterdam , The Netherlands. 2. b Department of Neonatology , Erasmus MC - Sophia Children's Hospital , Rotterdam , The Netherlands. 3. c Department of Development and Regeneration , KU , Leuven , Belgium. 4. d Paediatric Pharmacology and Pharmacometrics , University of Basel Children's Hospital , Basel , Switzerland. 5. e Division of Clinical Pharmacology , Children's National Health System , Washington , DC , USA.
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.
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.
Authors: A Kontou; K Sarafidis; O Begou; H G Gika; A Tsiligiannis; K Ogungbenro; A Dokoumetzidis; E Agakidou; E Roilides Journal: Antimicrob Agents Chemother Date: 2020-03-24 Impact factor: 5.191