Stratified Management for Bacterial Infections in Late Preterm and Term Neonates: Current Strategies and Future Opportunities Toward Precision Medicine.

Fleur M Keij,Karel Allegaert,René F Kornelisse,Annemarie M C Van Rossum,Gerdien A Tramper-Stranders,Niek B Achten,Irwin K M Reiss

doi:10.3389/fped.2021.590969

Abstract

Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influence treatment requirement and success rate. However, currently, many neonates are treated following a “one size fits all” approach, based on general protocols and standard antibiotic treatment regimens. Precision medicine has emerged in the last years and is perceived as a new, holistic, way of stratifying patients based on large-scale data including patient characteristics and disease specific features. Specific to sepsis, differences in disease susceptibility, disease severity, immune response and pharmacokinetics and -dynamics can be used for the development of treatment algorithms helping clinicians decide when and how to treat a specific patient or a specific subpopulation. In this review, we highlight the current and future developments that could allow transition to a more precise manner of antibiotic treatment in late preterm and term neonates, and propose a research agenda toward precision medicine for neonatal bacterial infections.

Highlights

Neonatal Bacterial Sepsis and InfectionsBacterial infection can lead to sepsis, a state in which dysregulation of the hosts’ response to the infection leads to potentially fatal organ dysfunction [1]
This paper will acknowledge the limitations of this proxy definition by incorporating the uncertainties it carries when making clinical decisions, Stratified Management for Neonatal Infections demonstrating how precision medicine can help with those decisions and highlighting how a future consensus definition can further advance precision medicine in treating neonatal sepsis [2, 3]
The incidence and mortality remain much higher among extreme preterm neonates, the absolute number of cases of Early-onset sepsis (EOS) is higher among late preterm- and term neonates, since prematurity (GA < 37 weeks) affects about 11% of total live births of which 85% occurs in the late preterm period (GA 32–37 weeks) [8]

Summary

BACKGROUND

Bacterial infection can lead to sepsis, a state in which dysregulation of the hosts’ response to the infection leads to potentially fatal organ dysfunction [1]. A decrease in HRV in combination with the presence of transient decelerations has showed to be an early predictor for sepsis and has led to the development of a heart rate characteristics (HRC) monitor This monitor can be used to identify patients at risk for developing LOS in the 24 h, allowing timely initiation of antibiotic therapy [86]. Several small pharmacokinetic studies have evaluated the use of oral antibiotics in neonatal infections and absorption is slower compared to that of older children and adults and inter-individual variation is seen, target levels can be reached following oral administration [121]. The algorithm has recently made available as a mobile application (NeoPInS app; Apple app store/Android) and can be used in daily clinic as support tool in late preterm and term neonates with suspected EOS

A RESEARCH AGENDA TOWARD PRECISION MEDICINE

Findings

CONCLUSIONS