Register      Login
Microbiology Australia Microbiology Australia Society
Microbiology Australia, bringing Microbiologists together
RESEARCH ARTICLE

Clinical application of bacteriophages in Europe

Jean-Paul Pirnay A B , Daniel De Vos A and Gilbert Verbeken A
+ Author Affiliations
- Author Affiliations

A Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, B-1120 Brussels, Belgium

B Tel: +32 2 2644844, Email: jean-paul.pirnay@mil.be

Microbiology Australia 40(1) 8-15 https://doi.org/10.1071/MA19010
Published: 28 February 2019

Abstract

Bacteriophages could help address the antibiotic resistance crisis that impacts health systems all over the world. In 2011, the European Commission formally confirmed that phage products used as therapeutics are medicinal products and thus manufacturers need to navigate the extremely arduous and enormously expensive medicine development and marketing pathway. However, up until now, not one therapeutic phage product has made it to the European market, and yet clinicians are under increasing pressure to use phages in the treatment of multidrug-resistant bacterial infections. While a handful of small European enterprises are struggling to squeeze therapeutic phage products through the conventional and centralised European medicinal products funnel, some clinicians and academics are exploring (European) national solutions to accelerate the availability of phages for the treatment of an increasing number of desperate patients. This mini-review summarises the actual status and perspectives of clinical phage application in Europe.


References

[1]  Abedon, S.T. et al. (2011) Phage treatment of human infections. Bacteriophage 1, 66–85.
Phage treatment of human infections.Crossref | GoogleScholarGoogle Scholar | 22334863PubMed |

[2]  Pirnay, J.P. et al. (2012) Introducing yesterday’s phage therapy in tomorrow’s medicine. Future Virol. 7, 379–390.
Introducing yesterday’s phage therapy in tomorrow’s medicine.Crossref | GoogleScholarGoogle Scholar |

[3]  Huys, I. et al. (2013) Paving a regulatory pathway for phage therapy. Europe should muster the resources to financially, technically and legally support the introduction of phage therapy. EMBO Rep. 14, 951–954.
Paving a regulatory pathway for phage therapy. Europe should muster the resources to financially, technically and legally support the introduction of phage therapy.Crossref | GoogleScholarGoogle Scholar | 24136414PubMed |

[4]  Verbeken, G. et al. (2012) Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine. Arch. Immunol. Ther. Exp. (Warsz.) 60, 161–172.
Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.Crossref | GoogleScholarGoogle Scholar | 22527355PubMed |

[5]  Pirnay, J.P. et al. (2011) The phage therapy paradigm: prêt-à-porter or sur-mesure? Pharm. Res. 28, 934–937.
The phage therapy paradigm: prêt-à-porter or sur-mesure?Crossref | GoogleScholarGoogle Scholar | 21063753PubMed |

[6]  Verbeken, G. et al. (2014) Call for a dedicated European legal framework for bacteriophage therapy. Arch. Immunol. Ther. Exp. (Warsz.) 62, 117–129.
Call for a dedicated European legal framework for bacteriophage therapy.Crossref | GoogleScholarGoogle Scholar | 24500660PubMed |

[7]  Rohde, C. et al. (2018) Expert opinion on three phage therapy related topics: bacterial phage resistance, phage training and prophages in bacterial production strains. Viruses 10, 178.
Expert opinion on three phage therapy related topics: bacterial phage resistance, phage training and prophages in bacterial production strains.Crossref | GoogleScholarGoogle Scholar |

[8]  Debarbieux, L. et al. (2016) A bacteriophage journey at the European Medicines Agency. FEMS Microbiol. Lett. 363, fnv225.
A bacteriophage journey at the European Medicines Agency.Crossref | GoogleScholarGoogle Scholar | 26656541PubMed |

[9]  Wright, A. et al. (2009) A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin. Otolaryngol. 34, 349–357.
A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.Crossref | GoogleScholarGoogle Scholar | 19673983PubMed |

[10]  Jault, P. et al. (2019) Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect. Dis. 19, 35–45.
Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial.Crossref | GoogleScholarGoogle Scholar | 30292481PubMed |

[11]  Servick, K. (2016) Beleaguered phage therapy trial presses on. Science 352, 1506.
Beleaguered phage therapy trial presses on.Crossref | GoogleScholarGoogle Scholar | 27339963PubMed |

[12]  Frank, C. et al. (2011) Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N. Engl. J. Med. 365, 1771–1780.
Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.Crossref | GoogleScholarGoogle Scholar | 21696328PubMed |

[13]  Brüssow, H. (2012) What is needed for phage therapy to become a reality in Western medicine? Virology 434, 138–142.
What is needed for phage therapy to become a reality in Western medicine?Crossref | GoogleScholarGoogle Scholar | 23059181PubMed |

[14]  Vogt, D. et al. (2017) Beyond antibiotic therapy – future antiinfective strategies – update 2017. Unfallchirurg 120, 573–584.
Beyond antibiotic therapy – future antiinfective strategies – update 2017.Crossref | GoogleScholarGoogle Scholar | 28643099PubMed |

[15]  Jennes, S. et al. (2017) Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury – a case report. Crit. Care 21, 129.
Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury – a case report.Crossref | GoogleScholarGoogle Scholar | 28583189PubMed |

[16]  Górski, A. et al. (2009) Bacteriophage therapy for the treatment of infections. Curr. Opin. Investig. Drugs 10, 766–774.
| 19649921PubMed |

[17]  Verbeken, G. et al. (2007) European regulatory conundrum of phage therapy. Future Microbiol. 2, 485–491.
European regulatory conundrum of phage therapy.Crossref | GoogleScholarGoogle Scholar | 17927471PubMed |

[18]  Międzybrodzki, R. et al. (2012) Clinical aspects of phage therapy. Adv. Virus Res. 83, 73–121.
Clinical aspects of phage therapy.Crossref | GoogleScholarGoogle Scholar | 22748809PubMed |

[19]  Patey, O. et al. (2019) Clinical indications and compassionate use of phage therapy: personal experience and literature review with a focus on osteoarticular infections. Viruses 11, 18.
Clinical indications and compassionate use of phage therapy: personal experience and literature review with a focus on osteoarticular infections.Crossref | GoogleScholarGoogle Scholar |

[20]  Dvořáčková, M. et al. (2019) Antimicrobial effect of commercial phage preparation Stafal® on biofilm and planktonic forms of methicillin-resistant Staphylococcus aureus. Folia Microbiol. (Praha) 64, 121–126.
Antimicrobial effect of commercial phage preparation Stafal® on biofilm and planktonic forms of methicillin-resistant Staphylococcus aureus.Crossref | GoogleScholarGoogle Scholar | 29923129PubMed |

[21]  van Nood, E. et al. (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415.
Duodenal infusion of donor feces for recurrent Clostridium difficile.Crossref | GoogleScholarGoogle Scholar | 23323867PubMed |

[22]  Pirnay, J.P. et al. (2018) The magistral phage. Viruses 10, 64.
The magistral phage.Crossref | GoogleScholarGoogle Scholar |

[23]  Fauconnier, A. (2017) Regulating phage therapy: the biological master file concept could help to overcome regulatory challenge of personalized medicines. EMBO Rep. 18, 198–200.
Regulating phage therapy: the biological master file concept could help to overcome regulatory challenge of personalized medicines.Crossref | GoogleScholarGoogle Scholar | 28082313PubMed |

[24]  Svircev, A. et al. (2018) Framing the future with bacteriophages in agriculture. Viruses 10, 218.
Framing the future with bacteriophages in agriculture.Crossref | GoogleScholarGoogle Scholar |

[25]  Moelling, K. et al. (2018) A wake-up call: we need phage therapy now. Viruses 10, 688.
A wake-up call: we need phage therapy now.Crossref | GoogleScholarGoogle Scholar |

[26]  Pires, D.P. et al. (2016) Genetically engineered phages: a review of advances over the last decade. Microbiol. Mol. Biol. Rev. 80, 523–543.
Genetically engineered phages: a review of advances over the last decade.Crossref | GoogleScholarGoogle Scholar | 27250768PubMed |