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Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections

The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosi...

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Autores principales: Arrazuria, Rakel, Kerscher, Bernhard, Huber, Karen E., Hoover, Jennifer L., Lundberg, Carina Vingsbo, Hansen, Jon Ulf, Sordello, Sylvie, Renard, Stephane, Aranzana-Climent, Vincent, Hughes, Diarmaid, Gribbon, Philip, Friberg, Lena E., Bekeredjian-Ding, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493304/
https://www.ncbi.nlm.nih.gov/pubmed/36160186
http://dx.doi.org/10.3389/fmicb.2022.988725
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author Arrazuria, Rakel
Kerscher, Bernhard
Huber, Karen E.
Hoover, Jennifer L.
Lundberg, Carina Vingsbo
Hansen, Jon Ulf
Sordello, Sylvie
Renard, Stephane
Aranzana-Climent, Vincent
Hughes, Diarmaid
Gribbon, Philip
Friberg, Lena E.
Bekeredjian-Ding, Isabelle
author_facet Arrazuria, Rakel
Kerscher, Bernhard
Huber, Karen E.
Hoover, Jennifer L.
Lundberg, Carina Vingsbo
Hansen, Jon Ulf
Sordello, Sylvie
Renard, Stephane
Aranzana-Climent, Vincent
Hughes, Diarmaid
Gribbon, Philip
Friberg, Lena E.
Bekeredjian-Ding, Isabelle
author_sort Arrazuria, Rakel
collection PubMed
description The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosing regimens and progressing drug candidates into the clinic. The Innovative Medicines Initiative-funded “Collaboration for prevention and treatment of MDR bacterial infections” (COMBINE) consortium is establishing a validated and globally harmonized preclinical model to increase reproducibility and more reliably translate results from animals to humans. Toward this goal, in April 2021, COMBINE organized the expert workshop “Advancing toward a standardized murine model to evaluate treatments for AMR lung infections”. This workshop explored the conduct and interpretation of mouse infection models, with presentations on PK/PD and efficacy studies of small molecule antibiotics, combination treatments (β-lactam/β-lactamase inhibitor), bacteriophage therapy, monoclonal antibodies and iron sequestering molecules, with a focus on the major Gram-negative AMR respiratory pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Here we summarize the factors of variability that we identified in murine lung infection models used for antimicrobial efficacy testing, as well as the workshop presentations, panel discussions and the survey results for the harmonization of key experimental parameters. The resulting recommendations for standard design parameters are presented in this document and will provide the basis for the development of a harmonized and bench-marked efficacy studies in preclinical murine pneumonia model.
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spelling pubmed-94933042022-09-23 Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections Arrazuria, Rakel Kerscher, Bernhard Huber, Karen E. Hoover, Jennifer L. Lundberg, Carina Vingsbo Hansen, Jon Ulf Sordello, Sylvie Renard, Stephane Aranzana-Climent, Vincent Hughes, Diarmaid Gribbon, Philip Friberg, Lena E. Bekeredjian-Ding, Isabelle Front Microbiol Microbiology The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosing regimens and progressing drug candidates into the clinic. The Innovative Medicines Initiative-funded “Collaboration for prevention and treatment of MDR bacterial infections” (COMBINE) consortium is establishing a validated and globally harmonized preclinical model to increase reproducibility and more reliably translate results from animals to humans. Toward this goal, in April 2021, COMBINE organized the expert workshop “Advancing toward a standardized murine model to evaluate treatments for AMR lung infections”. This workshop explored the conduct and interpretation of mouse infection models, with presentations on PK/PD and efficacy studies of small molecule antibiotics, combination treatments (β-lactam/β-lactamase inhibitor), bacteriophage therapy, monoclonal antibodies and iron sequestering molecules, with a focus on the major Gram-negative AMR respiratory pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Here we summarize the factors of variability that we identified in murine lung infection models used for antimicrobial efficacy testing, as well as the workshop presentations, panel discussions and the survey results for the harmonization of key experimental parameters. The resulting recommendations for standard design parameters are presented in this document and will provide the basis for the development of a harmonized and bench-marked efficacy studies in preclinical murine pneumonia model. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9493304/ /pubmed/36160186 http://dx.doi.org/10.3389/fmicb.2022.988725 Text en Copyright © 2022 Arrazuria, Kerscher, Huber, Hoover, Lundberg, Hansen, Sordello, Renard, Aranzana-Climent, Hughes, Gribbon, Friberg and Bekeredjian-Ding. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Arrazuria, Rakel
Kerscher, Bernhard
Huber, Karen E.
Hoover, Jennifer L.
Lundberg, Carina Vingsbo
Hansen, Jon Ulf
Sordello, Sylvie
Renard, Stephane
Aranzana-Climent, Vincent
Hughes, Diarmaid
Gribbon, Philip
Friberg, Lena E.
Bekeredjian-Ding, Isabelle
Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title_full Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title_fullStr Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title_full_unstemmed Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title_short Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
title_sort expert workshop summary: advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493304/
https://www.ncbi.nlm.nih.gov/pubmed/36160186
http://dx.doi.org/10.3389/fmicb.2022.988725
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