Omadacycline Compared to Vancomycin When Combined with Germinants To Disrupt the Life Cycle of Clostridioides difficile

Clostridioides difficile infections (CDI) are commonly treated with antibiotics that do not impact the dormant spore form of the pathogen. CDI-directed antibiotics, such as vancomycin and metronidazole, can destroy the vegetative form of C. difficile and protective microbiota. After treatment, spores can germinate into vegetative cells, causing clinical disease relapse and further spore shedding. This in vitro study compares the combination of germinants with vancomycin or omadacycline to antibiotics alone in eradicating C. difficile spores and vegetative cells. Among the four strains in this study, omadacycline MICs (0.031 to 0.125 mg/liter) were lower than vancomycin MICs (1 to 4 mg/liter). Neither omadacycline nor vancomycin in medium alone reduced spore counts. In three of the four strains, including the epidemic ribotype 027, spore eradication with germinants was 94.8 to 97.4% with vancomycin and 99.4 to 99.8% with omadacycline (P < 0.005). In ribotype 012, either antibiotic combined with germinants resulted in 100% spore eradication at 24 h. The addition of germinants with either antibiotic did not result in significant toxin A or B production, which was below the limit of detection (< 1.25 ng/ml) by 48 h. Limiting the number of spores present in patient gastrointestinal tracts at the end of therapy may be effective at preventing recurrent CDI and limiting spore shedding in the health care environment. These results with germinants warrant safety and efficacy evaluations in animal models.

Automated summary

Clostridioides difficile infections are commonly treated with antibiotics, but these do not impact the dormant spore form of the pathogen. This study found that combining germinants with omadacycline was more effective in eradicating spores compared to vancomycin, showing potential for preventing recurrent CDI and limiting spore shedding in healthcare settings.