Individualized precision dosing approaches to optimize antimicrobial therapy in pediatric populations

ABSTRACT

Introduction

Severe infections continue to impose a major burden on critically ill children and mortality rates remain stagnant. Outcomes rely on accurate and timely delivery of antimicrobials achieving target concentrations in infected tissue. Yet, developmental aspects, disease-related variables, and host factors may severely alter antimicrobial pharmacokinetics in pediatrics. The emergence of antimicrobial resistance increases the need for improved treatment approaches.

Areas covered

This narrative review explores why optimization of antimicrobial therapy in neonates, infants, children, and adolescents is crucial and summarizes the possible dosing approaches to achieve antimicrobial individualization. Finally, we outline a roadmap toward scientific evidence informing the development and implementation of precision antimicrobial dosing in critically ill children.

The literature search was conducted on PubMed using the following keywords: neonate, infant, child, adolescent, pediatrics, antimicrobial, pharmacokinetic, pharmacodynamic target, Bayes dosing software, optimizing, individualizing, personalizing, precision dosing, drug monitoring, validation, attainment, and software implementation. Further articles were sought from the references of the above searched articles.

Expert opinion

Recently, technological innovations have emerged that enabled the development of individualized antimicrobial dosing approaches in adults. More work is required in pediatrics to make individualized antimicrobial dosing approaches widely operationalized in this population.

KEYWORDS:

• Antimicrobial
• critically ill
• dosing software
• individualization
• infection
• model-informed precision dosing
• optimization
• pediatrics
• pharmacokinetics
• precision

Article highlights

• Antimicrobial exposure varies largely in pediatrics with wider PK intra- and inter-patient variability during critical illness

• Model-informed precision dosing (MIPD) such as Bayesian forecasting dosing software, which incorporates PK-PD population models may be utilized to optimize antimicrobial exposure in pediatric populations

• Current gaps in the literature exist, including a standardized approach in constructing PK-PD models, quality control in MIPD, particularly the requirement for external model validation and robust research to link PK-PD indices with clinical outcomes in pediatrics

• Implementation of MIPD into clinical practice calls for the collaboration between academics, government regulators, software providers, healthcare executives, hospital IT personnel, and clinicians.

• Antimicrobial precision dosing through the use of MIPD software is gaining increasing popularity and will become part of routine clinical practice in the decades to come

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not directly funded. The authors have acknowledged the University of Queensland scholarship supports (Research Training Program Tuition Fee Offset and Research Training Program Stipend).