A newer generation tetracycline antibiotic could be new weapon against C diff bacteria

Phase 1 trial shows new RX Fights C Diff and spares healthy microbiota.

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Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. CDI pathophysiology includes a significant disruption of gut microbiota, usually by broad-spectrum antibiotics, leading to loss of colonization resistance to C difficile.

New drug development for CDI-directed antibiotics is needed. In a phase-one human clinical trial, a researcher from the University of Houston, who is also a pharmacist, has shown that Omadacycline, a newer generation tetracycline antibiotic, could be a promising tool in fighting against the resilient bacteria Clostridioides difficile (C diff).

In the clinical trials, Omadacycline was found to cause a low likelihood of C diff. However, the reason behind this remains unknown.

For this study, scientists assessed the pharmacokinetics and gut microbiome effects of oral Omadacycline in comparison to Vancomycin. They found that when given orally, Omadacycline achieves high concentration in the gut and the effect on the gut microbiome, the healthy bacteria that lives in the colon.

Kevin Garey, Robert L. Boblitt Endowed Professor of Drug Discovery at the UH College of Pharmacy, said, “Our research shows off the coolness of the microbiome. Omadacycline caused a distinctly different effect on the microbiome than Vancomycin. This could explain why Omadacycline is a safe drug to give to patients at high risk for C diff infection. This could become a new method in drug development to see if antibiotics are not only killing the bacteria causing infections (the bad bugs) but not causing harm to the beneficial microbes that live in our body (the good bugs).”

“I would hope that this becomes a normal part of the antibiotic drug development process.”

The study involved 16 healthy volunteers who tolerated Omadacycline well, showing no safety differences compared to the other antibiotic. There was a rapid initial increase in the fecal concentration of Omadacycline compared to Vancomycin, with maximum concentrations achieved within 48 hours. This rapid increase is considered beneficial as it indicates that the active drug is reaching the site of the infection faster.

Garey said“Both the Omadacycline and Vancomycin groups showed significant changes in their microbiomes when we looked at how diverse they were internally (alpha diversity). However, when we compared the changes between the two groups (beta diversity), they were noticeably different from each other.”

Journal Reference:

  1. Jinhee Jo, Chenlin Hu, Khurshida Begum, et al. Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers. The Journal of Infectious Diseases. DOI: 10.1093/infdis/jiad537

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