Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler

Brieuc Van Nieuwenhuyse (), Dimitri Van der Linden, Olga Chatzis, Cédric Lood, Jeroen Wagemans, Rob Lavigne, Kaat Schroven, Jan Paeshuyse, Catherine de Magnée, Etienne Sokal, Xavier Stéphenne, Isabelle Scheers, Hector Rodriguez-Villalobos, Sarah Djebara, Maya Merabishvili, Patrick Soentjens and Jean-Paul Pirnay
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Brieuc Van Nieuwenhuyse: Université catholique de Louvain - UCLouvain
Dimitri Van der Linden: Université catholique de Louvain - UCLouvain
Olga Chatzis: Université catholique de Louvain - UCLouvain
Cédric Lood: Laboratory of Gene Technology, KU Leuven
Jeroen Wagemans: Laboratory of Gene Technology, KU Leuven
Rob Lavigne: Laboratory of Gene Technology, KU Leuven
Kaat Schroven: Laboratory of Gene Technology, KU Leuven
Jan Paeshuyse: KU Leuven
Catherine de Magnée: Cliniques universitaires Saint-Luc
Etienne Sokal: Cliniques universitaires Saint-Luc
Xavier Stéphenne: Cliniques universitaires Saint-Luc
Isabelle Scheers: Cliniques universitaires Saint-Luc
Hector Rodriguez-Villalobos: Cliniques universitaires Saint-Luc / Université catholique de Louvain - UCLouvain
Sarah Djebara: Queen Astrid Military Hospital
Maya Merabishvili: Queen Astrid Military Hospital
Patrick Soentjens: Queen Astrid Military Hospital
Jean-Paul Pirnay: Queen Astrid Military Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Post-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses – viruses who specifically prey on bacteria, naturally found in various environmental samples – as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.

Date: 2022
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DOI: 10.1038/s41467-022-33294-w

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