A new weapon against C. diff bacteria

In a phase-one human clinical trial, a US pharmacist researcher has demonstrated that a newer generation tetracycline antibiotic, called Omadacycline, may be a promising tool in combating the resilient bacteria Clostridioides difficile (C. diff), which causes an infection often picked up in hospitals. The bacteria brings on diarrhoea and colitis, an inflammation of the colon.

Clostridioides difficile infection (CDI) diagnosis in Australian public hospitals has increased year on year since 2014, according to the Australian Commission on Safety and Quality in Health Care. In 2014, the average number of all CDI diagnoses was 518 cases per month and the average number of CDI diagnoses went up to 677 cases per month in 2019.

The fight against C. diff takes its toll internally, including a significant disruption of gut microbiota, usually by broad-spectrum antibiotics, leading to loss of colonisation resistance to C. difficile. Omadacycline demonstrated a low likelihood of causing C. diff in clinical trials, but no one understood why.

Kevin Garey, Robert L. Boblitt Endowed Professor of Drug Discovery at the UH College of Pharmacy, assessed the pharmacokinetics and gut microbiome effects of oral Omadacycline in comparison to Vancomycin, another possible C. diff drug.

Vancomycin is used to treat C. diff but is said to be not good at eliminating it over the long term. Garey’s team investigated whether Omadacycline, given orally, achieves high concentration in the gut and the effect on the gut microbiome, the healthy bacteria that live in the colon.

“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),” said Garey, whose results were published in The Journal of Infectious Diseases. “I would hope that this becomes a normal part of the antibiotic drug development process.”

In the study, 16 healthy volunteers tolerated Omadacycline with no safety differences compared to the other antibiotic. A rapid initial increase in faecal concentration of Omadacycline was observed compared to Vancomycin, with maximum concentrations achieved within 48 hours. Rapid increase is a good thing — it means the active drug is getting to the site of the infection faster.

“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,” Garey reported.

Garey’s team includes Jinhee Jo, assistant professor, University of Houston College of Pharmacy; and Blake M Hanson and Hossaena Ayele, The University of Texas Health Science Center at Houston School of Public Health.

Image credit: University of Houston.