Clostridium difficile: New antibiotic can clear C diff and prevent reinfection

A new antibiotic is not only more effective than our first-line treatments Clostridium difficile According to the study done on rats, it also reduces the risk of infection to a great extent.

c difficult Causes symptoms including abdominal cramps, diarrhea and fever, and in extreme cases severe dehydration and kidney failure. kill about this kind of infection 13,000 people every year in America alone.

For this reason, it is one of five antibiotic-resistant infections currently listed by the US Centers for Disease Control and Prevention (CDC). “immediate threat”,But its deadline is really a class of its own.

,Clostridium difficile Infections result in more than seven times as many deaths as the remaining four CDC immediate threats combined,” says myland chang at the University of Notre Dame in Indiana and lead author of the study that identified the new antibiotic.

c difficult Infects the gut, often after people have taken antibiotics to clear up another infection. This can wipe out their gut microbiome by allowing c difficult To get acclimatized, often when people in hospital inhale airborne spores.

The first-line antibiotic, vancomycin, works well for initial infections, but becomes less effective after that.

“Vancomycin has no activity against spores and recurrence c difficult Infection remains a major problem after a course of vancomycin,” says Alexander Khoruts at the University of Minnesota.

This means that bacterial spores can live quietly in the body and cause infection for years. about 25 percent of people who have one c difficult Infections will lead to a second infection, 40 percent of people who have one recurrence will have a second, and 65 percent of those who have two recurrences will have a third, says Chang.

He and his group sought to break the cycle of re-infection. By selecting from a virtual database of anti-bacterial molecules, they isolated two compounds: oxadiazole 1 and oxadiazole 2. Oxidiazole 1 and 2 both killed c difficult In in vitro Tested at concentrations similar to vancomycin.

Oxadiazole is rapidly absorbed into the bloodstream. But this poses a problem for gut infections – the drug needs to stay in the gut. Oxadiazole 2 rapidly released into the blood, and the team discarded it. However, oxadiazole 1 remained stable. in a series of c difficult In infection studies, oxadiazole 1 protected mice from death about 30 percent better than vancomycin. Infected mice that received oxadiazole 1 lost weight within three to five days, where as vancomycin-treated mice were underweight for weeks after the initial infection.

But perhaps the most promising result was the way the drug stopped frequent infections. oxadiazole 1 blocks two c difficult Proteins that help bacteria form drug-resistant spores. After three weeks of treatment, mice that received vancomycin still had detectable spores in their feces and were prone to repeated infections. Mice treated with oxadiazole 1 had no quantifiable spores and no reinfections occurred during the study period.

Another treatment that has shown promise is fecal microbiota transplantation (FMT), where faeces from a healthy patient are used to re-establish a normal gut microbiome. Two commercially available FMT-based drugs were recently approved by the Food and Drug Administration, but they are not always effective.

“We need entirely new drug development” for a cure c difficultKhoruts says.