New Antibiotic Against Hospital-Acquired Superbug C. diff Shows Promise in Phase-One Clinical Trial

In a University of Houston-led phase-one clinical trial, the antibiotic Omadacycline showed promise against the hospital-acquired superbug C diff, known for causing infections. This modern tetracycline displayed a low risk of inducing C diff in trials, though the reasons remain unclear.

What Is Hospital-Acquired C. Diff Infection

Clostridioides difficile, commonly referred to as C. difficile or C. diff, is a bacterium responsible for causing infections in the colon, the longest part of the large intestine. The symptoms of C. difficile infection range from diarrhea to severe damage to the colon and can pose life-threatening risks.

The infection is often associated with the use of antibiotic medicines and primarily affects older adults in hospitals or long-term care settings, although it can also impact individuals outside of such environments. Certain strains of the bacterium, which can lead to serious infections, are more likely to affect younger people.

The onset of symptoms typically occurs within 5 to 10 days after initiating antibiotic treatment, with manifestations appearing as early as the first day or as late as three months later.

Mild to moderate C. difficile infections are characterized by watery diarrhea occurring three or more times a day for over one day, accompanied by mild belly cramping and tenderness. In severe cases, individuals may experience dehydration, requiring hospitalization.

Severe C. difficile infection can lead to inflammation of the colon, resulting in symptoms such as frequent watery diarrhea, intense abdominal cramping, a rapid heart rate, dehydration, fever, nausea, increased white blood cell count, kidney failure, loss of appetite, a swollen belly, weight loss, and the presence of blood or pus in the stool. While toxic megacolon and sepsis are potential complications of severe and sudden C. difficile infections, they are relatively uncommon.

Omadacycline vs. Vancomycin in C diff Treatment

Conducting a comparative study, Kevin Garey, the Robert L. Boblitt Endowed Professor of Drug Discovery at the UH College of Pharmacy, explored the pharmacokinetics and impact on the gut microbiome of oral Omadacycline and Vancomycin, a potential C diff treatment.

Despite being a C diff therapy, Vancomycin's long-term effectiveness is limited. The investigation aimed to ascertain whether orally administered Omadacycline attains high gut concentrations and influences the gut microbiome.

The study, titled "Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers" published in The Journal of Infectious Diseases, disclosed distinctive effects of Omadacycline on the microbiome compared to Vancomycin, potentially elucidating Omadacycline's safety in high-risk C diff patients.

This observation suggests a potential shift in antibiotic development standards, emphasizing the assessment of impacts on both harmful and beneficial bacteria. The research advocates the integration of such evaluations into routine antibiotic development processes.

Involving 16 healthy volunteers, the study indicated that Omadacycline was well-tolerated with no discernible safety differences compared to Vancomycin. Notably, Omadacycline exhibited a swift increase in fecal concentration, achieving maximum levels within 48 hours. This rapid escalation signifies the effective delivery of the active drug to the infection site.

Although both Omadacycline and Vancomycin groups experienced significant changes in internal microbiome diversity (alpha diversity), comparing these alterations (beta diversity) revealed notable distinctions between the two antibiotic groups. Garey's findings underscore the potential of Omadacycline as a promising and microbiome-friendly option in addressing C diff infections.

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