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

TY - JOUR

T1 - Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study

AU - Pirnay, Jean-Paul

AU - Djebara, Sarah

AU - Steurs, Griet

AU - Griselain, Johann

AU - Cochez, Christel

AU - De Soir, Steven

AU - Glonti, Tea

AU - Spiessens, An

AU - Vanden Berghe, Emily

AU - Green, Sabrina

AU - Wagemans, Jeroen

AU - Lood, Cédric

AU - Schrevens, Eddie

AU - Chanishvili, Nina

AU - Kutateladze, Mzia

AU - de Jode, Mathieu

AU - Ceyssens, Pieter-Jan

AU - Draye, Jean-Pierre

AU - Verbeken, Gilbert

AU - De Vos, Daniel

AU - Rose, Thomas

AU - Onsea, Jolien

AU - Van Nieuwenhuyse, Brieuc

AU - Bacteriophage Therapy Providers

AU - Bacteriophage Donors

AU - Soentjens, Patrick

AU - Lavigne, Rob

AU - Merabishvili, Maya

AU - Paul, Kevin

N1 - © 2024. The Author(s).

PY - 2024/6

Y1 - 2024/6

N2 - 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 .

AB - 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 .

KW - Humans

KW - Retrospective Studies

KW - Phage Therapy/methods

KW - Bacteriophages/physiology

KW - Female

KW - Male

KW - Middle Aged

KW - Anti-Bacterial Agents/therapeutic use

KW - Adult

KW - Bacterial Infections/therapy

KW - Treatment Outcome

KW - Aged

KW - Precision Medicine/methods

KW - Adolescent

KW - Young Adult

KW - Bacteria/virology

KW - Child

KW - Aged, 80 and over

KW - Child, Preschool

KW - Belgium

KW - Infant

U2 - 10.1038/s41564-024-01705-x

DO - 10.1038/s41564-024-01705-x

M3 - SCORING: Journal article

C2 - 38834776

VL - 9

SP - 1434

EP - 1453

JO - NAT MICROBIOL

JF - NAT MICROBIOL

SN - 2058-5276

IS - 6

ER -