Artificial Intelligence to Close the Gap between Pharmacokinetic/Pharmacodynamic Targets and Clinical Outcomes in Critically Ill Patients: A Narrative Review on Beta Lactams

João Gonçalves Pereira, Joana Fernandes, Tânia Mendes, Filipe André Gonzalez, Susana M. Fernandes
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Abstract

Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host’s immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of β-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment.
人工智能缩小重症患者药代动力学/药效学目标与临床结果之间的差距:关于β-内酰胺类药物的叙述性综述
抗菌药物剂量是一项复杂的挑战。尽管抗生素暴露与疗效之间存在着坚实的联系,但相互矛盾的数据表明,药代动力学/药效学目标与感染控制之间的相关性很差。导致这种差异的原因可能有多种:炎症和组织灌注不足导致β-内酰胺类药物的组织穿透性差;细菌对抗生素和生物膜的反应不同;宿主免疫反应和药物代谢的异质性;治疗过程中细菌的耐受性和耐药性的获得。因此,无论是固定剂量的抗生素还是固定的目标浓度,都可能注定失败。生物标志物在了解和监测宿主对感染反应方面的作用也尚未完全明确。如今,随着医院收集的数据流不断增长,利用最有效的分析工具可以更好地实现个性化治疗。人工智能和机器学习的兴起使大量数据得以快速访问和分析。这些无监督学习模型可以理解数据结构并识别同质子群,从而促进医疗干预的个性化。本综述旨在讨论β-内酰胺类药物剂量所面临的挑战,重点关注其药效学以及整合机器学习算法为患者提供个性化治疗所带来的新挑战和新机遇。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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