Currently running consortial projects, both under consultancy with the German licensing authority BfArM, Bonn:
Phage4Cure (http://phage4cure.de/de/), the first German publicly funded project aiming at a clinical trial with the development of purified phages as inhalative therapy against Pseudomonas aeruginosa in bronchiectasis. Phage4Cure is the first scientific study applying licensed GMP preparations containing phages as active pharmaceutical ingredients (APIs) in Germany. Project start: September 2017, duration of project: 3 years (extended), funding 100% by the BMBF, project partners: Leibniz-Institute DSMZ, Fraunhofer ITEM (Coordinator), Charité University hospital Berlin, Charité Research Organisation GmbH Berlin.
PhagoFlow (www.phagoflow.de/en/), the first German publicly funded practicability testing project for the magistral use of GMP-purified phage preparations against prioritized bacteria of the ESKAPE group. In contrast to a clinical trial, PhagoFlow will apply individualized combinations of efficiently working phages in single patient cases, predominantly in deep infected wounds where antibiotics have failed. A sustainable routine method for applying phagograms in hospital diagnostic labs will be developed to determine the most efficient phage mixture per patient. Project start: April 2019, duration of project: 3 years (extended), funding 100% by Innovationsausschuss des Gemeinsamen Bundesausschusses, project partners: Leibniz-Institute DSMZ, Fraunhofer ITEM, Bundeswehrkrankenhaus Berlin (Coordinator),
IDEAL-EC (Identification and evaluation of a phage cocktail with high lytic activity against Escherichia coli including extended-spectrum beta-lactamase (ESBL) producing isolates) is the first German preclinical study with explicit focus on the investigation of phage efficiency on E. coli isolates from hematological and oncological patients as such patients are especially at high risk of bloodstream infections. A large diversity of E. coli strains originating from previous national and international clinical studies are being retrieved for finding new, highly lytic phages. The project aims at combining them into a cocktail for application on clinical E. coli isolates and at providing the phage cocktail for subsequent preclinical gut model studies. Project start: April 2021, duration of project: 1.5 years, funding by the German Center for Infection Research (DZIF), project partners: Leibniz-Institute DSMZ, University Hospitals Cologne (leading coordination) and Frankfurt/Main.
EVREA-Phage The project EVREA-Phage (DZIF funding started in July 2022) aims to provide phage therapy for intestinal VRE reduction, especially for immunosuppressed patients. It envisages to characterize (bacterio)phages and compose one phage cocktail directed against E. faecium for later oral phage application whether in liquid or in capsular form. More information here
Selected references:
Weissfuss C, Wienhold S-M, Bürkle M, Gaborieau B, Bushe J, Behrendt U, Bischoff R, Korf IHE, Wienecke S, Dannheim A, Ziehr H, Rohde C, Gruber AD, Ricard J-D, Debarbieux L, Witzenrath M, Nouailles G (2023) Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naive Mice. Viruses 15, 387. doi:10.3390/v15020387.
Wienhold S-M, Brack MC, Nouailles G, Krishnamoorthy G, Korf IHE, Seitz C, Wienecke S, Dietert K, Gurtner C, Kershaw O, Gruber AD, Ross A, Ziehr H, Rohde M, Neudecker J, Lienau J, Suttorp N, Hippenstiel S, Hocke AC, Rohde C, Witzenrath M (2021) Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection. Viruses 2022, 14, 33. doi: 10.3390/v14010033.
Korf IHE, Meier-Kolthoff JP, Adriaenssens EM, Kropinski AM, Nimtz M, Rohde M, van Raaij MJ, Wittmann J. (2019) Still Something to Discover: Novel Insights into Escherichia coli Phage Diversity and Taxonomy 17;11(5). pii: E454, doi: 10.3390/v11050454.
Rohde C, Wittmann J, Kutter E (2018) Bacteriophages: A Therapy Concept against Multi-Drug-Resistant Bacteria. Surg Infect (Larchmt). 19:737-744, doi: 10.1089/sur.2018.184.
Sybesma W, Rohde C, Bardy P, Pirnay JP, Cooper I, Caplin J, Chanishvili N, Coffey A, De Vos D, Scholz AH, McCallin S, Püschner HM, Pantucek R, Aminov R, Doškař J, Kurtbӧke Dİ (2018) Expert round table on acceptance and re-implementation of bacteriophage therapy. Silk Route to the Acceptance and Re-Implementation of Bacteriophage Therapy-Part II. Antibiotics (Basel). 7(2). pii: E35, doi: 10.3390/antibiotics7020035.
