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噬菌体治疗肺部感染:来自临床经验的教训和关键考虑因素。

Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations.

机构信息

Division of Pulmonology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland

University of Lausanne, Lausanne, Switzerland.

出版信息

Eur Respir Rev. 2022 Oct 5;31(166). doi: 10.1183/16000617.0121-2022. Print 2022 Dec 31.


DOI:10.1183/16000617.0121-2022
PMID:36198417
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9724797/
Abstract

Lower respiratory tract infections lead to significant morbidity and mortality. They are increasingly caused by multidrug-resistant pathogens, notably in individuals with cystic fibrosis, hospital-acquired pneumonia and lung transplantation. The use of bacteriophages (phages) to treat bacterial infections is gaining growing attention, with numerous published cases of compassionate treatment over the last few years. Although the use of phages appears safe, the lack of standardisation, the significant heterogeneity of published studies and the paucity of robust efficacy data, alongside regulatory hurdles arising from the existing pharmaceutical legislation, are just some of the challenges phage therapy has to overcome. In this review, we discuss the lessons learned from recent clinical experiences of phage therapy for the treatment of pulmonary infections. We review the key aspects, opportunities and challenges of phage therapy regarding formulations and administration routes, interactions with antibiotics and the immune system, and phage resistance. Building upon the current knowledge base, future pre-clinical studies using emerging technologies and carefully designed clinical trials are expected to enhance our understanding and explore the therapeutic potential of phage therapy.

摘要

下呼吸道感染会导致严重的发病率和死亡率。它们越来越多地由多药耐药病原体引起,尤其是在囊性纤维化、医院获得性肺炎和肺移植患者中。利用噬菌体(phages)治疗细菌感染的方法越来越受到关注,在过去几年中已经有许多同情治疗的案例发表。尽管噬菌体的使用似乎是安全的,但缺乏标准化、发表研究的显著异质性以及缺乏稳健的疗效数据,以及现有药物立法带来的监管障碍,只是噬菌体治疗需要克服的一些挑战。在这篇综述中,我们讨论了从最近的临床经验中吸取的教训噬菌体治疗用于治疗肺部感染。我们回顾了噬菌体治疗在制剂和给药途径、与抗生素和免疫系统的相互作用以及噬菌体耐药性方面的关键方面、机会和挑战。在现有知识库的基础上,未来使用新兴技术和精心设计的临床试验的临床前研究有望增强我们的理解并探索噬菌体治疗的治疗潜力。

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Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations.

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引用本文的文献

[1]
Inhalable nanoparticle-based delivery systems for the treatment of pulmonary infections: and barrier-overcoming strategies.

Drug Deliv. 2025-12

[2]
A novel genus of virulent phage targeting Acinetobacter baumannii: Efficacy and safety in a murine model of pulmonary infection.

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[3]
Clinical translation of microbiome research.

Nat Med. 2025-4

[4]
Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant -induced pulmonary infection.

Emerg Microbes Infect. 2025-12

[5]
Phage therapy for extensively drug resistant infection: case report and evaluation of the distribution of phage and the impact on gut microbiome.

Front Med (Lausanne). 2024-12-20

[6]
Engineering Phages to Fight Multidrug-Resistant Bacteria.

Chem Rev. 2025-1-22

[7]
The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

JCI Insight. 2024-10-22

[8]
Phage Therapy: An Alternative Approach to Combating Multidrug-Resistant Bacterial Infections in Cystic Fibrosis.

Int J Mol Sci. 2024-7-30

[9]
Cystic fibrosis.

Nat Rev Dis Primers. 2024-8-8

[10]
Phage Therapy for Respiratory Infections: Opportunities and Challenges.

Lung. 2024-6

本文引用的文献

[1]
Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection.

Cell. 2022-5-26

[2]
Bacteriophage treatment of disseminated cutaneous Mycobacterium chelonae infection.

Nat Commun. 2022-5-3

[3]
Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review.

Lancet Infect Dis. 2022-8

[4]
Parallel evolution of phage resistance and virulence loss in response to phage treatment in vivo and in vitro.

Elife. 2022-2-21

[5]
Mitigation of evolved bacterial resistance to phage therapy.

Curr Opin Virol. 2022-4

[6]
The effects of different doses of inhaled bacteriophage therapy for Pseudomonas aeruginosa pulmonary infections in mice.

Clin Microbiol Infect. 2022-7

[7]
Considerations for the Use of Phage Therapy in Clinical Practice.

Antimicrob Agents Chemother. 2022-3-15

[8]
Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections.

Front Cell Infect Microbiol. 2021

[9]
Survival Comes at a Cost: A Coevolution of Phage and Its Host Leads to Phage Resistance and Antibiotic Sensitivity of Multidrug Resistant Strains.

Front Microbiol. 2021-12-2

[10]
Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial.

Am J Respir Crit Care Med. 2022-3-1

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