Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study
Authors: Pirnay Jean-Paul , Djebara Sarah , Steurs Griet , Griselain Johann , Cochez Christel , De Soir Steven , Glonti Tea , Spiessens An , Vanden Berghe Emily , Green Sabrina , Wagemans Jeroen , Lood Cédric , Schrevens Eddie , Chanishvili Nina , Kutateladze Mzia , de Jode Mathieu , Ceyssens Pieter-Jan , Draye Jean-Pierre , Verbeken Gilbert , De Vos Daniel , Rose Thomas , Onsea Jolien , Van Nieuwenhuyse Brieuc ,   Bacteriophage Therapy Providers, Pang Kim Win , Metsemakers Willem-Jan , Van der Linden Dimitri , Chatzis Olga , Eskenazi Anaïs , Lopez Angel , De Voeght Adrien , Rousseau Anne Françoise , Tilmanne Anne , Vens Daphne , Gérain Jean , Layeux Brice , Vlieghe Erika , Baar Ingrid , Van Ierssel Sabrina , Van Laethem Johan , Guiot Julien , De Roock Sophie , Jennes Serge , Uyttebroek Saartje , Van Gerven Laura , Hellings Peter W. , Dupont Lieven , Debaveye Yves , Devolder David , Spriet Isabel , De Munter Paul , Depypere Melissa , Vanfleteren Michiel , Cornu Olivier , Verhulst Stijn , Boiy Tine , Lamote Stoffel , Van Zele Thibaut , Wieërs Grégoire , Courtin Cécile , Lebeaux David , Sartre Jacques , Ferry Tristan , Laurent Frédéric , Paul Kevin , Di Luca Mariagrazia , Gottschlich Stefan , Tkhilaishvili Tamta , Cesta Novella , Racenis Karlis , Barbosa Telma , López-Cortés Luis Eduardo , Tomás Maria , Hübner Martin , Pham Truong-Thanh , Nagtegaal Paul , Ten Oever Jaap , Daniels Johannes , Loubert Maartje , Iheb Ghariani , Jones Joshua , Hall Lesley , Young Matthew ,   Bacteriophage Donors, Balarjishvili Nana , Tediashvili Marina , Tong Yigang , Rohde Christine , Wittmann Johannes , Hazan Ronen , Nir-Paz Ran , Azeredo Joana , Krylov Victor , Cameron David , Pitton Melissa , Que Yok-Ai , Resch Gregory , McCallin Shawna , Dunne Matthew , Kilcher Samuel , Soentjens Patrick , Lavigne Rob , Merabishvili Maya 
Published: June 2024

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127–0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage–antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363.