Silk route to the acceptance and re‐implementation of bacteriophage therapy

Sybesma, Wilbert; Pirnay, Jean‐Paul; Alavidze, Zemphira; Aminov, Rustam; Betts, Alexander; Bardiau, Marjorie; Bretaudeau, Laurent; Caplin, Jonathan; Chanishvili, Nina; Coffey, Aidan; Cooper, Ian; Vos, Daniël De; Doškař, Jiřı́; Friman, Ville‐Petri; Hoyle, Naomi; Karanadze, Nino; Kurtböke, D. İpek; Kutateladze, Mzia; McCallin, Shawna; Merabishvili, Maya; Mgaloblishvili, George; Nadareishvili, Lia; Nikolaishvili, Nikoloz; Nizharadze, Dea; Pantůček, Roman; Resch, Grégory; Rohde, Christine; Shulaia, Teona; Тедиашвили, Марина; Ujmajuridze, Aleksandre

doi:10.1002/biot.201600023

Cited by 53 publications

(28 citation statements)

References 17 publications

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“…Prior to these steps, it is necessary to maintain an adequately robust development pipeline along with strategies toward regulatory approval. Presently, phage therapy is relatively extensively used only in three countries, Georgia, Poland, and Russia, while its acceptance and re-implementation in other countries is still pending (Expert Round Table on Acceptance and Re-Implementation of Bacteriophage Therapy, 2016). As discussed by Cooper et al, difficulties with acceptance are due to: (i) differences in biological, physical, and pharmacological properties of phages compared to conventional antimicrobials, (ii) the need to employ multiple phage isolates (cocktails) due to the high specificity of phages (thereby allowing for more effective presumptive treatment, that is, treatment which is initiated prior to precise diagnosis of microbial etiologies), and (iii) current approval processes for antimicrobial agents that are based on chemically derived drugs and which consequently are less suitable for phages.…”

Section: The Current State Of Phage Therapy Implementationmentioning

confidence: 99%

Editorial: Phage Therapy: Past, Present and Future

et al. 2017

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Section: The Current State Of Phage Therapy Implementationmentioning

confidence: 99%

Editorial: Phage Therapy: Past, Present and Future

et al. 2017

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“…In 2017 the current Phagoburn clinical trial evaluating phage therapy in the treatment of burn wounds infected with E. coli and P. aeruginosa should be completed, while Technophage has received FDA clearance to begin a trial of a phage cocktail for the treatment of infected chronic ulcers occurring in diabetic foot infections. New data on the efficacy of phage therapy are therefore on the horizon; however, new clinical trials addressing important clinical dilemmas (e.g., urinary tract infections) are urgently needed ( Chan et al, 2013 ; Ly-Chatain, 2014 ; Letkiewicz, 2015 ; Pirnay et al, 2015 ; Vandenheuvel et al, 2015 ; Young and Gill, 2015 ; Chanishvili, 2016 ; Debarbieux et al, 2016 ; Expert round table on acceptance and re-implementation of bacteriophage therapy, 2016 ; Verbeken et al, 2016 ).…”

Section: Clinical Trials Vs Observational Studies and Experimental Tmentioning

confidence: 99%

Phage Therapy: Combating Infections with Potential for Evolving from Merely a Treatment for Complications to Targeting Diseases

et al. 2016

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Antimicrobial resistance is considered to be one of the greatest challenges of medicine and our civilization. Lack of progress in developing new anti-bacterial agents has greatly revived interest in using phage therapy to combat antibiotic-resistant infections. Although a number of clinical trials are underway and more are planned, the realistic perspective of registration of phage preparations and their entering the health market and significantly contributing to the current antimicrobial crisis is rather remote. Therefore, in addition to planning further clinical trials, our present approach of phage treatment carried out as experimental therapy (compassionate use) should be expanded to address the growing and urgent needs of increasing cohorts of patients for whom no alternative treatment is currently available. During the past 11 years of our phage therapy center’s operation, we have obtained relevant clinical and laboratory data which not only confirm the safety of the therapy but also provide important information shedding more light on many aspects of the therapy, contributing to its optimization and allowing for construction of the most appropriate clinical trials. New data on phage biology and interactions with the immune system suggest that in the future phage therapy may evolve from dealing with complications to targeting diseases. However, further studies are necessary to confirm this promising trend.

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“…Phage therapy continues in Russia and Eastern Europe to this day ( Expert Round Table on Acceptance and Therapy Re-implementation of Bacteriophage, 2016 ). In the West, phage therapy was revived in the 1980s by Smith and Huggins in a series of carefully controlled experiments using systemic Escherichia coli and Enterotoxigenic E. coli (ETEC) infections in mice, calves, pigs, and sheep ( Smith and Huggins, 1980 , 1982 , 1983 ; Smith et al, 1987a , b ).…”

Section: Introductionmentioning

confidence: 99%

Biology and Genomics of an Historic Therapeutic Escherichia coli Bacteriophage Collection

et al. 2017

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We have performed microbiological and genomic characterization of an historic collection of nine bacteriophages, specifically infecting a K1 E. coli O18:K1:H7 ColV+ strain. These phages were isolated from sewage and tested for their efficacy in vivo for the treatment of systemic E. coli infection in a mouse infection model by Smith and Huggins (1982). The aim of the study was to identify common microbiological and genomic characteristics, which co-relate to the performance of these phages in in vivo study. These features will allow an informed selection of phages for use as therapeutic agents. Transmission electron microscopy showed that six of the nine phages were Podoviridae and the remaining three were Siphoviridae. The four best performing phages in vivo belonged to the Podoviridae family. In vitro, these phages exhibited very short latent and rise periods in our study. In agreement with their microbiological profiles, characterization by genome sequencing showed that all six podoviruses belong to the Autographivirinae subfamily. Of these, four were isolates of the same species (99% identity), whereas two had divergent genomes compared to other podoviruses. The Siphoviridae phages, which were moderate to poor performers in vivo, exhibited longer latent and rise periods in vitro. Two of the three siphoviruses were closely related to each other (99% identity), but all can be associated with the Guernseyvirinae subfamily. Genome sequence comparison of both types of phages showed that a gene encoding for DNA-dependent RNA polymerase was only present in phages with faster replication cycle, which may account for their better performance in vivo. These data define a combination of microbiological, genomic and in vivo characteristics which allow a more rational evaluation of the original in vivo data and pave the way for the selection of phages for future phage therapy trails.

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Silk route to the acceptance and re‐implementation of bacteriophage therapy

Abstract: of all mentioned stakeholders, especially (supra)national authorities in their role as definitive stakeholder, on how to develop an infrastructure and legislation that paves the way for the acceptance and re-implementation of bacteriophage therapy.

Cited by 53 publications

References 17 publications

Editorial: Phage Therapy: Past, Present and Future

Editorial: Phage Therapy: Past, Present and Future

Phage Therapy: Combating Infections with Potential for Evolving from Merely a Treatment for Complications to Targeting Diseases

Biology and Genomics of an Historic Therapeutic Escherichia coli Bacteriophage Collection

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