Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
JournalNature Microbiology
DOIs
StateAccepted/In press - 2024
Externally publishedYes

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Publisher Copyright:
© The Author(s) 2024.

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