噬菌体鸡尾酒对耐药大肠菌素肺炎克雷伯氏菌引起的小鼠尿路感染的评估

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Journal of global antimicrobial resistance Pub Date : 2024-08-18 DOI:10.1016/j.jgar.2024.07.019
Alakh Narayan Singh , Aprajita Singh , Gopal Nath
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引用次数: 0

摘要

目的:耐大肠菌素的肺炎克雷伯氏菌会导致复杂的尿路感染(UTI)。其中,73%的肺炎克雷伯菌株会形成中度至高度生物膜。引起UTI的耐多药(MDR)/耐潘多拉(PDR)细菌对传统抗生素疗法极具挑战性。然而,噬菌体可能是一种很有前景的替代疗法,因为它们很容易破坏生物膜,并作用于与抗生素耐药性机制无关的受体。这项临床前研究评估了不同途径和剂量(数量和频率)的噬菌体鸡尾酒在小鼠模型中根除肺炎克氏菌相关UTI的疗效:方法:利用扫描电镜和测序技术对三种具有最广谱活性的致死噬菌体(ΦKpnBHU1、ΦKpnBHU2和ΦKpnBHU3)进行了细致的表征。用对碳青霉烯类和可乐定均耐药的肺炎双球菌(KpnBHU09)建立UTI后,通过尿道、直肠、皮下和口服途径给小鼠注射鸡尾酒。我们对不同给药途径、不同给药剂量和不同给药频率的疗效进行了全面优化:我们观察到,在尿道口注射两剂含 1 × 105 菌斑形成单位(PFU/小鼠)的噬菌体鸡尾酒和单剂含 1 × 109 PFU/小鼠的噬菌体鸡尾酒可根除 KpnBHU09。耐人寻味的是,通过口服和直肠途径进行非侵入性给药需要更高浓度和更多剂量的噬菌体,才能在急性UTI的任何阶段消灭KpnBHU09。结论:结论:通过经尿道、口服和直肠途径给药的噬菌体鸡尾酒可治愈UTI。
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Evaluation of bacteriophage cocktail on urinary tract infection caused by colistin-resistant Klebsiella pneumoniae in mice model

Objective

The colistin-resistant Klebsiella pneumoniae causes complicated urinary tract infections (UTIs). Of them, 73% of strains of K. pneumoniae formed moderate to strong biofilm. Multidrug-resistant (MDR)/Pandrug-resistant (PDR) bacteria causing UTIs are very challenging to conventional antibiotic therapy. However, bacteriophages may be a promising alternative as they easily disrupt the biofilm and act on receptors unrelated to antibiotic resistance mechanisms. This preclinical study evaluated the efficacy of a phage cocktail with different routes and dosages (in quantity and frequency) to eradicate the K. pneumoniae-associated UTI in the mice model.

Methods

The three lytic phages with the broadest spectrum activity (ΦKpnBHU1, ΦKpnBHU2 and ΦKpnBHU3) were meticulously characterized using SEM and sequencing. The cocktails were administered to mice through urethral, rectal, subcutaneous and oral routes after establishing the UTI with 1 × 108 colony-forming unit/mouse (CFU/mouse) of K. pneumoniae (KpnBHU09) resistant to both the drugs carbapenem and colistin. The efficacy of different routes with varying dosages and frequency of administration was thoroughly optimized.

Results

We observed that two doses of a phage cocktail containing 1 × 105 Plaque-Forming Unit (PFU/mouse) and a single dose of 1 × 109 PFU/mouse per urethra could eradicate KpnBHU09. Intriguingly, the non-invasive administration through oral and rectal routes required higher concentration and many dosages of phages to eliminate KpnBHU09 at any stage of acute UTI. The subcutaneous route was found unsatisfactory in curing the infection.

Conclusion

Bacteriophage cocktails administered through transurethral, oral and rectal routes may cure UTIs.

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来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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