New Drug Targets C. diff Infection

First in New Class of Antibiotics Being Tested Against Diarrhea Bug

By Charlene Laino
WebMD Health News

Reviewed By Louise Chang, MD

Sept.16, 2009 (San Francisco) -- Researchers are developing a novel antibiotic that they hope can help turn the tide in the epidemic of the nasty bug Clostridium difficile, or C. diff.

Dubbed NVB302, the drug is the first in a new class of antibiotics called Type B lantibiotics to undergo testing against C. diff.

NVB302 successfully killed C. diff in test tube studies and prolonged survival in hamsters infected with the bacterium. Novacta Biosystems, the company developing the drug, hopes to start human studies within a year, says Michael J. Dawson, MD, chief scientific officer.

C. Diff: the Epidemic

The potentially dangerous diarrhea bug causes several hundred thousand human infections and several thousand deaths each year in the United States, according to the CDC.

In recent years, the number and severity of these infections has been on the rise, says Curtis Donskey, MD, an infectious diseases specialist at Case Western Reserve University in Cleveland.

"Cases have tripled in the last few years," he tells WebMD.

Most cases of C. diff occur in people taking so-called broad spectrum antibiotics that kill many different types of pathogens.

Spores enter the body through the mouth, which is the entryway for the gastrointestinal tract. The broad spectrum antibiotics kill "good" bacteria in the gut that keep C. diff at bay.

The resulting overgrowth of the C. diff bacteria in the colon, or large intestine, can cause diarrhea, which is often severe and accompanied by intestinal inflammation known as colitis.

C. Diff: The New Drug

Other more selective antibiotics such as Vancocin and Flagyl are typically used to treat the infection, but many patients still suffer recurrences, says Sjoerd Wadman, PhD, director of therapeutic products at Novacta.

These drugs work in about 75% of patients, he says. "But after seemingly successful initial treatment, symptoms come back in some 20% to 25% of patients 10 to 30 days later," he tells WebMD.

Researchers don't fully understand why recurrences occur, but they believe that even these "selective" antibiotics sometimes kill off the "good" pathogens in the gut, Wadman says.

"New therapeutic approaches are urgently needed," he says.

That's where NVB302, which is given in tablet form, comes in. In test tube studies, "it targeted C. diff very selectively, allowing normal gut [bacteria] to recover," Wadman says.

In the animal studies, the researchers infected hamsters with C. diff. They also gave them the antibiotic clindamycin, which disturbed the normal gut flora and allowed C. diff to grow.

If the animals aren't treated further, they will die within 72 hours, Dawson says. But they lived much longer when given NVB302, he says.

The research was presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

C. Diff: Expert Comments

Now the company is conducting safety studies in healthy animals, a step required by the FDA before human testing can proceed.

One of the big advantages of the new drug is that the studies showed it is not significantly absorbed into the bloodstream after being given orally, says Karen Bush, PhD, an expert specializing in the development of new products for infectious diseases at Indiana University, Bloomington.

"This means it's less likely to affect the normal [healthy] bacteria [than other antibiotics]," she tells WebMD. Bush was not involved with the work.

SOURCES: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, Sept. 12-15, 2009. Michael J. Dawson, MD, chief scientific officer, Novacta Biosystems, Welwyn Garden City, U.K. Curtis Donskey, MD, Case Western Reserve University, Cleveland. Sjoerd Wadman, PhD, director of therapeutic products, Novacta Biosystems, Welwyn Garden City, U.K. Karen Bush, PhD, Indiana University, Bloomington.

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