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Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation

Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faeci...

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Autores principales: Paul, Kevin, Merabishvili, Maya, Hazan, Ronen, Christner, Martin, Herden, Uta, Gelman, Daniel, Khalifa, Leron, Yerushalmy, Ortal, Coppenhagen-Glazer, Shunit, Harbauer, Theresa, Schulz-Jürgensen, Sebastian, Rohde, Holger, Fischer, Lutz, Aslam, Saima, Rohde, Christine, Nir-Paz, Ran, Pirnay, Jean-Paul, Singer, Dominique, Muntau, Ania Carolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472888/
https://www.ncbi.nlm.nih.gov/pubmed/34578366
http://dx.doi.org/10.3390/v13091785
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author Paul, Kevin
Merabishvili, Maya
Hazan, Ronen
Christner, Martin
Herden, Uta
Gelman, Daniel
Khalifa, Leron
Yerushalmy, Ortal
Coppenhagen-Glazer, Shunit
Harbauer, Theresa
Schulz-Jürgensen, Sebastian
Rohde, Holger
Fischer, Lutz
Aslam, Saima
Rohde, Christine
Nir-Paz, Ran
Pirnay, Jean-Paul
Singer, Dominique
Muntau, Ania Carolina
author_facet Paul, Kevin
Merabishvili, Maya
Hazan, Ronen
Christner, Martin
Herden, Uta
Gelman, Daniel
Khalifa, Leron
Yerushalmy, Ortal
Coppenhagen-Glazer, Shunit
Harbauer, Theresa
Schulz-Jürgensen, Sebastian
Rohde, Holger
Fischer, Lutz
Aslam, Saima
Rohde, Christine
Nir-Paz, Ran
Pirnay, Jean-Paul
Singer, Dominique
Muntau, Ania Carolina
author_sort Paul, Kevin
collection PubMed
description Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faecium abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two Enterococcus phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient’s serum could be detected. Vancomycin-susceptible E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials.
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spelling pubmed-84728882021-09-28 Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation Paul, Kevin Merabishvili, Maya Hazan, Ronen Christner, Martin Herden, Uta Gelman, Daniel Khalifa, Leron Yerushalmy, Ortal Coppenhagen-Glazer, Shunit Harbauer, Theresa Schulz-Jürgensen, Sebastian Rohde, Holger Fischer, Lutz Aslam, Saima Rohde, Christine Nir-Paz, Ran Pirnay, Jean-Paul Singer, Dominique Muntau, Ania Carolina Viruses Article Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faecium abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two Enterococcus phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient’s serum could be detected. Vancomycin-susceptible E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials. MDPI 2021-09-07 /pmc/articles/PMC8472888/ /pubmed/34578366 http://dx.doi.org/10.3390/v13091785 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paul, Kevin
Merabishvili, Maya
Hazan, Ronen
Christner, Martin
Herden, Uta
Gelman, Daniel
Khalifa, Leron
Yerushalmy, Ortal
Coppenhagen-Glazer, Shunit
Harbauer, Theresa
Schulz-Jürgensen, Sebastian
Rohde, Holger
Fischer, Lutz
Aslam, Saima
Rohde, Christine
Nir-Paz, Ran
Pirnay, Jean-Paul
Singer, Dominique
Muntau, Ania Carolina
Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title_full Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title_fullStr Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title_full_unstemmed Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title_short Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation
title_sort bacteriophage rescue therapy of a vancomycin-resistant enterococcus faecium infection in a one-year-old child following a third liver transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472888/
https://www.ncbi.nlm.nih.gov/pubmed/34578366
http://dx.doi.org/10.3390/v13091785
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