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Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model

BACKGROUND: Clostridioides difficile infections (CDI) and recurrence (rCDI) are major health care burdens. Recurrence is likely caused by spores in the gastrointestinal tract that germinate after antibiotic therapy. This murine study explores germinant-antibiotic combinations for CDI. METHODS: Previ...

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Autores principales: Budi, Noah D, Godfrey, Jared J, Safdar, Nasia, Shukla, Sanjay K, Rose, Warren E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978312/
https://www.ncbi.nlm.nih.gov/pubmed/35904942
http://dx.doi.org/10.1093/infdis/jiac324
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author Budi, Noah D
Godfrey, Jared J
Safdar, Nasia
Shukla, Sanjay K
Rose, Warren E
author_facet Budi, Noah D
Godfrey, Jared J
Safdar, Nasia
Shukla, Sanjay K
Rose, Warren E
author_sort Budi, Noah D
collection PubMed
description BACKGROUND: Clostridioides difficile infections (CDI) and recurrence (rCDI) are major health care burdens. Recurrence is likely caused by spores in the gastrointestinal tract that germinate after antibiotic therapy. This murine study explores germinant-antibiotic combinations for CDI. METHODS: Previously described murine models were evaluated using C. difficile VPI 10463. The severe model compared omadacycline versus vancomycin in survival, weight loss, clinical scoring, and C. difficile toxin production. The nonsevere model compared these antibiotics with and without germinants (solution of sodium taurocholate, taurine, sodium docusate, calcium gluconate). Additionally, colon histopathology, bile acid analysis, environmental/spore shedding, and 16S sequencing was evaluated. RESULTS: In the severe model, omadacycline-treated mice had 60% survival versus 13.3% with vancomycin (hazard ratio [HR], 0.327; 95% confidence interval [CI],.126–.848; P = .015) along with decreased weight loss, and disease severity. In the nonsevere model, all mice survived with antibiotic-germinant treatment versus 60% antibiotics alone (HR, 0.109; 95% CI, .02–.410; P = .001). Omadacycline resulted in less changes in bile acids and microbiota composition. Germinant-treated mice showed no signs of rCDI, spore shedding, or significant toxin production at 15 days. CONCLUSIONS: In murine models of CDI, omadacycline improved survival versus vancomycin. Germinant-antibiotic combinations were more effective at preventing rCDI compared to antibiotics alone without inducing toxin production.
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spelling pubmed-99783122023-03-03 Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model Budi, Noah D Godfrey, Jared J Safdar, Nasia Shukla, Sanjay K Rose, Warren E J Infect Dis Major Article BACKGROUND: Clostridioides difficile infections (CDI) and recurrence (rCDI) are major health care burdens. Recurrence is likely caused by spores in the gastrointestinal tract that germinate after antibiotic therapy. This murine study explores germinant-antibiotic combinations for CDI. METHODS: Previously described murine models were evaluated using C. difficile VPI 10463. The severe model compared omadacycline versus vancomycin in survival, weight loss, clinical scoring, and C. difficile toxin production. The nonsevere model compared these antibiotics with and without germinants (solution of sodium taurocholate, taurine, sodium docusate, calcium gluconate). Additionally, colon histopathology, bile acid analysis, environmental/spore shedding, and 16S sequencing was evaluated. RESULTS: In the severe model, omadacycline-treated mice had 60% survival versus 13.3% with vancomycin (hazard ratio [HR], 0.327; 95% confidence interval [CI],.126–.848; P = .015) along with decreased weight loss, and disease severity. In the nonsevere model, all mice survived with antibiotic-germinant treatment versus 60% antibiotics alone (HR, 0.109; 95% CI, .02–.410; P = .001). Omadacycline resulted in less changes in bile acids and microbiota composition. Germinant-treated mice showed no signs of rCDI, spore shedding, or significant toxin production at 15 days. CONCLUSIONS: In murine models of CDI, omadacycline improved survival versus vancomycin. Germinant-antibiotic combinations were more effective at preventing rCDI compared to antibiotics alone without inducing toxin production. Oxford University Press 2022-07-29 /pmc/articles/PMC9978312/ /pubmed/35904942 http://dx.doi.org/10.1093/infdis/jiac324 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Budi, Noah D
Godfrey, Jared J
Safdar, Nasia
Shukla, Sanjay K
Rose, Warren E
Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title_full Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title_fullStr Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title_full_unstemmed Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title_short Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a Murine Model
title_sort efficacy of omadacycline or vancomycin combined with germinants for preventing clostridioides difficile relapse in a murine model
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978312/
https://www.ncbi.nlm.nih.gov/pubmed/35904942
http://dx.doi.org/10.1093/infdis/jiac324
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