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经支气管镜和雾化给药的噬菌体的安全性和耐受性。

Safety and tolerability of bronchoscopic and nebulised administration of bacteriophage.

机构信息

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Westmead Institute of Medical Research, Sydney, NSW, Australia.

出版信息

Virus Res. 2024 Oct;348:199442. doi: 10.1016/j.virusres.2024.199442. Epub 2024 Jul 31.

Abstract

INTRODUCTION

Pseudomonas aeruginosa is an organism well known for causing significant morbidity and mortality in people living with chronic lung conditions such as cystic fibrosis. We describe the safety, tolerability, and potential efficacy of bronchoscopic and nebulised bacteriophage administration, offering insights into a potential breakthrough for the treatment of chronic infections particularly in children and adolescents.

METHOD

A 12-year-old female (F12) and a 17-year-old male (M17), both diagnosed with cystic fibrosis and chronic P. aeruginosa lung infection, underwent bacteriophage treatment (BT). The administration involved bronchoscopic instillation and subsequent nebulisation. This was performed concurrently with intravenous antibiotics and regular physiotherapy delivered in an in-patient setting for 14 days. Microbiological, clinical, and lung function assessments were conducted to assess this treatment modality.

RESULTS

No adverse events (fever, localised reaction, wheeze or bronchospasm) occurred during BT. F12 demonstrated a 4% increase, while M17 showed a 5% improvement in FEV1% from their best FEV1% over the past three years following BT. A 12% (F12) and an 8% (M17) improvement from baseline FEV1% was observed. For F12 P. aeruginosa was not isolated from her sputum despite 12 previous hospitalisations for intravenous antibiotics.

CONCLUSION

Bronchoscopic and nebulised routes of bacteriophage administration were well-tolerated in these two adolescents. This early report underscores the potential of this treatment modality and encourages clinicians and researchers to actively explore this innovative approach.

摘要

简介

铜绿假单胞菌是一种众所周知的病原体,它会导致患有慢性肺部疾病(如囊性纤维化)的人群产生严重的发病率和死亡率。我们描述了支气管镜和雾化噬菌体给药的安全性、耐受性和潜在疗效,为治疗慢性感染提供了新的思路,特别是在儿童和青少年中。

方法

一名 12 岁的女性(F12)和一名 17 岁的男性(M17)均被诊断患有囊性纤维化和慢性铜绿假单胞菌肺部感染,接受了噬菌体治疗(BT)。给药途径包括支气管镜内注入和随后的雾化。这与静脉内抗生素和常规物理治疗同时进行,在住院环境中进行了 14 天。对微生物学、临床和肺功能进行了评估,以评估这种治疗方式。

结果

在 BT 过程中没有发生不良反应(发热、局部反应、喘息或支气管痉挛)。F12 的 FEV1%在过去三年中增加了 4%,而 M17 的 FEV1%则提高了 5%。F12 和 M17 的 FEV1%分别从基线提高了 12%和 8%。尽管 F12 曾因静脉内抗生素治疗而住院 12 次,但她的痰液中未分离出铜绿假单胞菌。

结论

支气管镜和雾化噬菌体给药途径在这两名青少年中耐受良好。这一早期报告强调了这种治疗方式的潜力,并鼓励临床医生和研究人员积极探索这种创新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cb1/11341935/0a6db19042a8/gr1.jpg

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