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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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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. |
format | Online Article Text |
id | pubmed-9978312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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