Pharmacokinetics and pharmacodynamics of bacteriophage therapy: a review with a focus on multidrug-resistant Gram-negative bacterial infections.

IF 19 1区 医学 Q1 MICROBIOLOGY Clinical Microbiology Reviews Pub Date : 2024-09-12 Epub Date: 2024-07-29 DOI:10.1128/cmr.00044-24
Maria Siopi, Dimitrios Skliros, Paschalis Paranos, Nikoletta Koumasi, Emmanouil Flemetakis, Spyros Pournaras, Joseph Meletiadis
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Abstract

SUMMARYDespite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host's immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their in vivo PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the in vitro PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, Klebsiella pneumoniae, Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Escherichia coli, specific data on in vivo PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.

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噬菌体疗法的药代动力学和药效学:以耐多药革兰氏阴性菌感染为重点的综述。
摘要尽管噬菌体的治疗潜力很早就得到了认可,而且目前耐多药(MDR)病原体不断增加,但由于不熟悉噬菌体的基本药代动力学(PK)和药效学(PD)等特性,噬菌体在主流临床实践中的应用受到了阻碍。鉴于噬菌体在宿主细菌存在下的自我复制特性、吸附率以及宿主免疫力的清除率,其 PK/PD 特性无法用传统方法估算,因此需要引入新的考虑因素。此外,由于噬菌体类型、制剂和治疗时间各不相同,因此无法对其体内 PK/PD 特征得出一般性结论。此外,还应考虑到 MDR 病原体对噬菌体产生耐药性的弊端对临床和环境的影响。在此,我们概述了噬菌体疗法的 PK 和 PD 领域的现状,重点介绍了其在治疗革兰氏阴性耐药菌感染方面的应用,并强调了在从实验室到临床转化过程中可能存在的知识差距和挑战。在回顾了噬菌体针对四种主要 MDR 革兰氏阴性病原体(肺炎克雷伯氏菌、鲍曼不动杆菌复合体、铜绿假单胞菌和大肠埃希菌)的体外 PKs 和 PDs 之后,总结了体内 PKs(组织分布、给药途径、动物和人类的基本 PK 参数)和 PDs(存活率和细菌负荷的减少与给药途径、治疗时机、给药方案和耐药性的关系)的具体数据。目前可用的数据值得仔细研究,当务之急是在更好地了解基本 PK/PD 原理的基础上优化噬菌体疗法,以提高其治疗效果并最大限度地减少噬菌体耐药性的发生。
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来源期刊
Clinical Microbiology Reviews
Clinical Microbiology Reviews 医学-微生物学
CiteScore
54.20
自引率
0.50%
发文量
38
期刊介绍: Clinical Microbiology Reviews (CMR) is a journal that primarily focuses on clinical microbiology and immunology.It aims to provide readers with up-to-date information on the latest developments in these fields.CMR also presents the current state of knowledge in clinical microbiology and immunology.Additionally, the journal offers balanced and thought-provoking perspectives on controversial issues in these areas.
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