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Published on: December 10, 2016
Efficacy of Omadacycline or Vancomycin Combined With Germinants for Preventing Clostridioides difficile Relapse in a
Noah D Budi1, Jared J Godfrey2,3, Nasia Safdar2,3
1School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA.
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.
Insights
New germinant-antibiotic combinations show promise in preventing recurrent Clostridioides difficile infections (CDI). Omadacycline improved survival in a murine model, and germinant combinations prevented recurrence without increasing toxin production.
Area of Science:
- Microbiology and Immunology
- Gastroenterology
- Pharmacology
Background:
- Clostridioides difficile infections (CDI) and recurrent CDI (rCDI) pose significant healthcare challenges.
- Recurrence is often linked to dormant spores germinating post-antibiotic treatment.
- Murine models are crucial for studying CDI pathogenesis and therapeutic interventions.
Purpose of the Study:
- To investigate the efficacy of novel germinant-antibiotic combinations in preventing CDI and rCDI.
- To compare omadacycline with vancomycin in a severe CDI murine model.
- To evaluate the impact of germinants on antibiotic effectiveness and CDI recurrence.
Main Methods:
- Utilized established murine models for CDI, comparing omadacycline and vancomycin.
- Administered antibiotics with and without germinants in a non-severe CDI model.
- Assessed survival, weight loss, clinical scores, toxin production, colon histopathology, bile acid profiles, and 16S rRNA sequencing.
Main Results:
- Omadacycline demonstrated superior survival rates (60%) compared to vancomycin (13.3%) in the severe CDI model.
- Antibiotic-germinant combinations achieved 100% survival in the non-severe model, versus 60% with antibiotics alone.
- Germinant treatment prevented rCDI, spore shedding, and toxin production without significant alterations in bile acids or microbiota.
Conclusions:
- Omadacycline offers improved survival outcomes in murine CDI models compared to vancomycin.
- Germinant-antibiotic combinations are highly effective in preventing rCDI recurrence.
- This approach shows potential for preventing CDI recurrence without exacerbating disease or altering the gut microbiome.
