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Cited by 474

The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.

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

Open access
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·2024·Nature Microbiology
DOI 10.1038/s41564-024-01705-x
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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 .

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Authors
Pirnay, J.-P., Djebara, S., Steurs, G., Griselain, J., Cochez, C., De Soir, S., Glonti, T., Spiessens, A., Vanden Berghe, E., Green, S., Wagemans, J., Lood, C., Schrevens, E., Chanishvili, N., Kutateladze, M., de Jode, M., Ceyssens, P.-J., Draye, J.-P., Verbeken, G., De Vos, D., Rose, T., Onsea, J., Van Nieuwenhuyse, B., Providers, B. T., Pang, K. W., Metsemakers, W.-J., Van der Linden, D., Chatzis, O., Eskenazi, A., Lopez, A., De Voeght, A., Rousseau, A. F., Tilmanne, A., Vens, D., Gérain, J., Layeux, B., Vlieghe, E., Baar, I., Van Ierssel, S., Van Laethem, J., Guiot, J., De Roock, S., Jennes, S., Uyttebroek, S., Van Gerven, L., Hellings, P. W., Dupont, L., Debaveye, Y., Devolder, D., Spriet, I., De Munter, P., Depypere, M., Vanfleteren, M., Cornu, O., Verhulst, S., Boiy, T., Lamote, S., Van Zele, T., Wieërs, G., Courtin, C., Lebeaux, D., Sartre, J., Ferry, T., Laurent, F., Paul, K., Di Luca, M., Gottschlich, S., Tkhilaishvili, T., Cesta, N., Racenis, K., Barbosa, T., López-Cortés, L. E., Tomás, M., Hübner, M., Pham, T.-T., Nagtegaal, P., Ten Oever, J., Daniels, J., Loubert, M., Iheb, G., Jones, J., Hall, L., Young, M., Donors, B., Balarjishvili, N., Tediashvili, M., Tong, Y., Rohde, C., Wittmann, J., Hazan, R., Nir-Paz, R., Azeredo, J., Krylov, V., Cameron, D., Pitton, M., Que, Y.-A., Resch, G., McCallin, S., Dunne, M., Kilcher, S., Soentjens, P., Lavigne, R., & Merabishvili, M.
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2024-06-04
Volume
9
Issue
6
Pages
1434-1453
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-024-01705-x
OpenAlex
W4399323029
Cited by
474
References
80
FWCI
126.32
Type
journal article
Language
en
Open access
hybrid

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Pirnay, J.-P., Djebara, S., Steurs, G., Griselain, J., Cochez, C., De Soir, S., Glonti, T., Spiessens, A., Vanden Berghe, E., Green, S., Wagemans, J., Lood, C., Schrevens, E., Chanishvili, N., Kutateladze, M., de Jode, M., Ceyssens, P.-J., Draye, J.-P., Verbeken, G., . . . Merabishvili, M. (2024). Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study. Nature Microbiology. https://doi.org/10.1038/s41564-024-01705-x

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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