Therapeutic Drug Monitoring of Antimicrobial Drugs in Neonates: An Opinion Article

Abstract

Background: Neonatal infections are associated with high morbidity and mortality rates. Optimal treatment of these infections requires knowledge of neonatal pharmacology and integration of neonatal developmental pharmacokinetics (PKs) of antimicrobial drugs in the design of dosing regimens for use with different gestational and postnatal ages. Population PK and pharmacodynamic models are used to personalize the use of these drugs in these fragile patients. The final step to further minimize variability in an individual patient is therapeutic drug monitoring (TDM), where the same population PK/pharmacodynamic models are used in concert with optimally drawn blood samples to further fine-tune therapy. The purpose of this article is to describe the present status and future role of model-based precision dosing and TDM of antimicrobial drugs in neonates. Methods: PubMed was searched for clinical trials or clinical studies of TDM in neonates.Results: A total of 447 articles were retrieved, of which 19 were concerned with antimicrobial drugs. Two articles (one aminoglycoside and one vancomycin) addressed the effects of TDM in neonates. We found that, in addition to aminoglycosides and vancomycin, TDM also plays a role in beta-lactam antibiotics and antifungal drugs.Conclusions: There is a growing awareness that, in addition to aminoglycosides and vancomycin, the use of beta-lactam antibiotics, such as amoxicillin and meropenem, and other classes of antimicrobial drugs, such as antifungal drugs, may benefit from TDM. However, the added value must be shown. New analytical techniques and software development may greatly support these novel developments.

Population PK/PD modelling of meropenem in preterm newborns based on therapeutic drug monitoring data

“…These age-related changes in PK were probably related to developmental changes associated with renal function and body composition. Our PK results support the previously described tendency ( Touw and van den Anker, 2022 ), that meropenem total body clearance in neonates is comparable with that in adults; however, the volume of distribution in neonates is significantly greater (for weight normalized estimates) ( Mouton et al, 2000 ; Li et al, 2006 ; Ganguly et al, 2021 ).…”

“…But each neonate had an individual speed of organ maturation, and pathophysiological changes could potentially increase intraindividual variability. Poor predictable meropenem PK in preterm newborns is a reason for TDM use ( Touw and van den Anker, 2022 ).…”

“…For neonates, it is also important to take into account descriptors of maturation of the organism, such as GA, PNA, PCA, postmenstrual age, body weight, etc. ( Germovsek et al (2018) ; Smith et al, 2011 ; Ganguly et al, 2021 ; Touw and van den Anker, 2022 ).…”

An Audit to Evaluate Vancomycin Therapeutic Drug Monitoring in a Neonatal Intensive Care Unit

“…9 Therapeutic drug monitoring (TDM) of vancomycin is, therefore, an important part of clinical decision-making, which helps improve clinical responses and reduce adverse effects. 10,11 Currently, there is a lack of consensus on vancomycin dosing guidelines for neonates. Empirical dosing recommendations range between 10 and 20 mg/kg every 8, 12, 18, or 24 hours, based on age, weight, or renal function.…”

Special Issue on the Therapeutic Drug Monitoring of Anti-infective Drugs: Editorial

“…Extrapolating standard dosing to the abovementioned special populations can result in suboptimal exposure because a variety of pathophysiological changes can occur in these patients and significantly alter drug pharmacokinetics (PK). The expanding role of therapeutic drug monitoring (TDM) as a tool to characterize drug PK and individualize antibiotic therapies in critically ill patients, 1–3 pregnant and lactating women, 4 individuals at both extremes of the age spectrum, 5,6 and patients undergoing complex dialysis procedures that include continuous renal replacement therapies 7 is highlighted in this special issue of TDM . In addition, Richter et al 8 discussed the key role of PK, pharmacodynamics (PD), and TDM within interprofessional antibiotic stewardship programs that have been implemented in clinical practice.…”