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

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. Alterna...

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Published in:Nature communications Vol. 13; no. 1; pp. 5725 - 12
Main Authors: Van Nieuwenhuyse, Brieuc, Van der Linden, Dimitri, Chatzis, Olga, Lood, Cédric, Wagemans, Jeroen, Lavigne, Rob, Schroven, Kaat, Paeshuyse, Jan, de Magnée, Catherine, Sokal, Etienne, Stéphenne, Xavier, Scheers, Isabelle, Rodriguez-Villalobos, Hector, Djebara, Sarah, Merabishvili, Maya, Soentjens, Patrick, Pirnay, Jean-Paul
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.09.2022
Nature Publishing Group
Nature Portfolio
Subjects:
45
45/23
631/326/1321
631/326/22/1434
64
692/308/575
692/699/1503/1607
692/699/255/1318
Antibiotic resistance
Antibiotics
Antibodies
Bacteria
Bacterial diseases
Bacterial infections
Combination therapy
Drug resistance
Failure
Humanities and Social Sciences
Infections
Intravenous administration
Liver
Liver transplantation
Liver transplants
Morbidity
multidisciplinary
Neutralization
Phages
Prey
Pseudomonas aeruginosa
Science
Science (multidisciplinary)
Sepsis
Therapy
Transplantation
Virulence
Viruses
ISSN:2041-1723, 2041-1723
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Summary: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. In this study, authors use combinatory bacteriophage-antibiotic therapy, as treatment for extensively drug-resistant Pseudomonas aeruginosa infection in a toddler post liver transplantation. They report on the clinical and microbiological improvement, and present their investigation on how bacterial phage resistance did not result in therapeutic failure.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33294-w