[en] 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 .
Disciplines :
Anesthesia & intensive care Immunology & infectious disease
Author, co-author :
Pirnay, Jean-Paul ; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium. jean-paul.pirnay@mil.be ; European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Non-traditional Antibacterial Therapy (ESGNTA), Basel, Switzerland. jean-paul.pirnay@mil.be
Djebara, Sarah; Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium
Steurs, Griet; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
Griselain, Johann; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
Cochez, Christel; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
De Soir, Steven; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
Glonti, Tea; Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
Spiessens, An; Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium
Vanden Berghe, Emily; Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium
Green, Sabrina ; Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium
Wagemans, Jeroen ; Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium
Lood, Cédric ; Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium
Schrevens, Eddie; Department of Biosystems, KU Leuven, Leuven, Belgium
Chanishvili, Nina; Eliava Institute of Bacteriophages, Microbiology and Virology, Tbilisi, Georgia
Kutateladze, Mzia ; Eliava Institute of Bacteriophages, Microbiology and Virology, Tbilisi, Georgia
de Jode, Mathieu; Bacterial Diseases, Sciensano, Brussels, Belgium
Rousseau, Anne-Françoise ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale ; Université de Liège - ULiège > Département des sciences cliniques ; Université de Liège - ULiège > Département des sciences de la santé publique ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs généraux
De Voeght, Adrien ; Université de Liège - ULiège > Département des sciences cliniques
Guiot, Julien ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study.
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