A new antibiotic effectively treats Clostridium difficile infections in mice and also helps prevent the formation of new spores (in yellow)
Jeshina Janardhanan and Yuanyuan Qian
A new antibiotic is not only more effective than our first-line treatments for Clostridium difficile infections, but it also significantly reduces the risk of reinfection, according to studies in mice.
It’s hard causes symptoms such as abdominal cramps, diarrhea and fever, and in extreme cases severe dehydration and kidney failure. These infections kill approximately 13,000 people each year in the United States alone.
For this reason, it is one of five antibiotic-resistant infections currently listed by the US Centers for Disease Control and Prevention (CDC) as “urgent threats”.”but his death is truly in a class of its own.
“Clostridium difficile infection causes more than seven times as many deaths as the CDC’s other four urgent threats combined,” says Mayland Chang of the University of Notre Dame in Indiana and lead author of the study identifying the new antibiotic.
It’s hard infects the gut, often after people have taken antibiotics to clear up another infection. This can eliminate their gut microbiota, allowing It’s hard to take hold, often when people inhale airborne spores in the hospital.
The first-line antibiotic, vancomycin, works well for initial infections but becomes less effective later.
“Vancomycin has no activity against spores and recurrence of It’s hard infection after a course of vancomycin remains a big problem,” says Alexander Khoruts of the University of Minnesota.
This means that spores of the bacteria can reside silently in the body and cause infection years later. About 25% of people infected with It’s hard going to get a second infection, Chang said. Forty percent of people who have a second infection will have a third, and 65% who have a third infection will have a fourth, she says.
She and her group sought to break the cycle of reinfection. They searched a database of antibacterial molecules, looking for compounds with activity against a specific type of binding protein in bacteria. This led them to two compounds: oxadiazole 1 and oxadiazole 2. in vitro tests, both compounds are killed It’s hard when applied at the same concentrations as vancomycin.
Oxadiazoles are rapidly absorbed into the bloodstream. But for intestinal infections, this is a problem – the drug must remain in the intestine. Oxadiazole 2 was quickly released into the mice’s blood, so the team pursued no further. Oxadiazole 1, however, stayed put. In a series of It’s hard infection studies, oxadiazole 1 protected mice from death about 30% better than vancomycin. Infected mice given oxadiazole 1 regained weight within three to five days, while vancomycin-treated mice were still underweight for weeks after the initial infection.
But perhaps the most promising result was how the drug stopped lingering infections. Oxadiazole 1 blocks two It’s hard proteins that help bacteria form drug-resistant spores. After three weeks of treatment, mice given vancomycin still had detectable spores in their faeces and continued to have recurrent infections. Mice treated with oxadiazole 1 had no quantifiable spores and had no reinfections during the study period.
The results may suggest a new way to treat C difference. infections in people. Another treatment that has shown promise is fecal microbiota transplantation (FMT), where people receive stool from an uninfected donor to restore healthy gut microbiota. Two commercially available FMT drugs have recently been approved by the Food and Drug Administration, but they are not always effective.
“We absolutely need to develop new drugs” to treat It’s hardKhoruts said.
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