Phage therapy is highly effective against chronic lung infections with<i>Pseudomonas aeruginosa</i>

Waters, Elaine M.; Neill, Daniel R.; Kaman, Basak; Sahota, Jaspreet Singh; Clokie, Martha R. J.; Winstanley, Craig; Kadioglu, Aras

doi:10.1136/thoraxjnl-2016-209265

Cited by 181 publications

(130 citation statements)

References 9 publications

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“…The overarching goal of each approach, however, focuses on how best to slow the emergence of resistance and control breakdown. Bacteriophages have been employed successfully in certain instances to treat animal 53–55 and plant 56 infections, and are thought to be particularly advantageous over traditional antibiotics because of their ability to amplify in the presence of their target host 57 and to overcome resistance through reciprocal coevolution. However, concerns remain, regarding the ability of phages ability to both promote horizontal gene transfer of potentially pathogenic determinants and to shift host tropism 58 .…”

Section: Discussionmentioning

confidence: 99%

Conditionally Redundant Bacteriocin Targeting byPseudomonas syringae

Clark

Scott

et al. 2017

Preprint

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Section: Discussionmentioning

confidence: 99%

Conditionally Redundant Bacteriocin Targeting byPseudomonas syringae

Clark

Scott

et al. 2017

Preprint

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“…Twelve hours after the administration of bacteriophages, bacterial cells in the mouse sputum were counted; in all cases, these counts were shown to be statistically lower than that in the control group (i.e. bacterial cells were not detected when bacteriophages were administered 24 and 36 h after inoculation; Waters et al ).…”

Section: Nonclinical Studiesmentioning

confidence: 98%

Therapeutic bacteriophages as a rescue treatment for drug‐resistant infections – anin vivostudies overview

Kwiatek

Parasion²,

Nakonieczna

2019

J Appl Microbiol

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Summary Bacteriophages, highly prevalent in all environments, have found their use in medicine as an alternative or complement to antibiotics. The therapeutic use of bacteriophages was particularly popular in the 1920s and 1930s, until the discovery and introduction of antibiotics. Due to the dynamic growth of antibiotic resistance among bacterial strains, numerous international institutions (such as the FDA) have declared the search for novel treatment modalities to be of the highest priority. To date, bacteriophage therapy has not been registered for general use in Western countries. The regulation of biological medicinal products (within medicinal product regulation) does not contain a specific documentation frame for bacteriophages (only for vaccines, blood derived products, etc.) which, as active substances, need to meet specific requirements. Recently, the FDA allowed bacteriophage therapy to be used in the United States, via the Emergency Investigational New Drug scheme; clinical trials to compare the safety and efficacy of bacteriophage therapy are also permitted. To date, several therapeutic products of this type have made it to phase I or II; some clinical programmes have also been completed. This article cites numerous animal model studies and registered clinical trials, showing the safety and effectiveness of bacteriophage therapy, including infections caused by bacterial strains resistant to antibiotic treatment.

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“…A recent research letter by Waters et al highlighted the potential of inhaled phages by demonstrating the effects of their administration on a murine model of chronic lung infection with an epidemic strain of P. aeruginosa. 106 They report a significant reduction in bacterial Colony Forming Units (CFU) from lung homogenate when phage was administered intranasally at a variety of time points ranging from 24 to 156 h post-infection. Several studies have reported the in vitro activity of phages against P. aeruginosa in biofilms isolated from the sputum of infected CF patients, where multidrug-resistant P. aeruginosa represents an increasing clinical problem.…”

Section: Phage Therapymentioning

confidence: 99%

Emerging therapies in adult and paediatric bronchiectasis

Regan

Hill

2018

Respirology

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Bronchiectasis is a chronic respiratory disorder characterized by persistent productive cough and recurrent chest infections secondary to permanent structural airway damage. The current treatment strategies for this debilitating disorder are limited to prompt antibiotic treatment of infective exacerbations and regular airway clearance techniques. Despite its high morbidity and associated mortality across all age groups, it has been a neglected area of research in respiratory medicine and there remain no licensed disease‐modifying therapies. In this review, we have explored the numerous potential therapeutic targets to break the vicious cycle of infection and inflammation seen in these patients and the novel therapeutic agents that have been developed to target them. We have reviewed the role of novel anti‐inflammatory agents designed to target the persistent neutrophilic inflammatory infiltrate seen in bronchiectatic airways, including neutrophil elastase inhibitors, CXCR2 (CXC chemokine receptor 2) antagonists, DPP‐1 (dipeptidyl peptidase 1) inhibitors, PDE4 (phosphodiesterase 4) inhibitors and statins. Furthermore, we have explored novel targets to improve mucociliary clearance, namely ENaC (epithelial sodium channel) inhibitors, and discussed the potential of alternative antimicrobial strategies such as inhaled phages. Our review highlights the importance of a multi‐faceted approach to bronchiectasis management, which aims not only to eradicate or suppress bronchial infection but also to break the cycle of persistent airway inflammation that results in progressive lung damage in these patients.

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Phage therapy is highly effective against chronic lung infections withPseudomonas aeruginosa

Cited by 181 publications

References 9 publications

Conditionally Redundant Bacteriocin Targeting byPseudomonas syringae

Conditionally Redundant Bacteriocin Targeting byPseudomonas syringae

Therapeutic bacteriophages as a rescue treatment for drug‐resistant infections – anin vivostudies overview

Emerging therapies in adult and paediatric bronchiectasis

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