Promising new antibiotic defies conventional wisdom on treating superbug

by Josh Barney

A new antibiotic being developed at the University of Virginia School of Medicine to combat the dangerous C. difficile superbug also appears effective against a wide array of other pathogens, including the Helicobacter pylori bacterium, a new study suggests. With antibiotic resistance a growing concern – and an alarming shortage of new antibiotics in development – the drug is notable because it works in a way that prevents microbes from becoming resistant to it.

U.Va.'s new findings challenge conventional wisdom that the best way to develop new treatments for Clostridium difficile, a growing problem in health care settings nationwide, is to target that infection specifically and to use an antibiotic that concentrates in the gut. U.Va.'s , Amixicile, does neither – yet early testing suggests it could be significantly more effective than existing options.

Sparing Good Gut Bacteria

Amixicile may prove particularly effective against C. difficile because, unlike other antibiotics, it spares beneficial probiotic and other beneficial bacteria. There is growing evidence to suggest that help prevent C. difficile re-infection and relapse, so antibiotics that concentrate in the gut and kill off the intestinal flora indiscriminately make it easier for C. difficile to regain a toehold. Mice infected with C. difficile that were treated with other commonly relapsed and died, but there were no relapses in mice treated with Amixicile, the researchers report.

Unlike other C. difficile therapeutics, Amixicile concentrates in the bloodstream, rather than in the gut, and emerges only at infected sites. Thus, Amixicile may be useful in treatment of systemic anaerobic and parasitic infections as well as gastric infections caused by H. pylori. More broadly, because of its low toxicity and immunity to mutation-based drug resistance, it potentially could be used as a lifelong prophylactic to prevent flare-ups of chronic diseases such as Crohn's disease and ulcerative colitis. It may even prove effective against anaerobes associated with periodontal disease.

"If the drug works even half as well as what we've found to date, there would be nothing like it in the existing antimicrobials," said Paul S. Hoffman of the U.Va. Division of Infectious Diseases and International Health and the Department of Microbiology, Immunology and Cancer Biology.

Overcoming Drug Resistance

Amixicile avoids the problem of mutation-based drug resistance by its unusual mechanism of action. Amixicile targets the function of the vitamin B1 cofactor of pyruvate, ferredoxin oxidoreductase, an enzyme uniquely found in anaerobic pathogens and not present in humans or in the probiotic beneficial gut bacteria.

The vitamin cofactor, a small molecule, is not susceptible to mutation, offering a remarkably reliable – and therefore very attractive – target. Because the target won't change, the risk of bacteria becoming resistant to the antibiotic is lessened dramatically.

Next Steps

More preclinical work needs to be done before the researchers can gain FDA approval to begin testing Amixicile in people. They next intend to evaluate maximum tolerable doses in animals and examine whether the drug has any genetic or mutagenic effects. If all goes well, they will eventually proceed to human testing.

The researchers' latest findings have been published online by Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology, and will appear in the August issue.

add to favorites email to friend print save as pdf

Related Stories

Probiotics prevent diarrhoea related to antibiotic use

May 30, 2013

Probiotic supplements have the potential to prevent diarrhoea caused by antibiotics, according to a new Cochrane systematic review. The authors studied Clostridium difficile (C. difficile) infections in patients taking antibi ...

Recommended for you

Mali announces new Ebola case

16 hours ago

Mali announced Saturday a new case of Ebola in a man who is fighting for his life in an intensive care unit in the capital Bamako.

Plague outbreak kills 40 in Madagascar: WHO

16 hours ago

An outbreak of plague has killed 40 people in Madagascar, the World Health Organization said, warning that the disease could spread rapidly in the country's densely populated capital Antananarivo.

UN chief: Ebola cases in Mali a 'deep concern'

Nov 21, 2014

The United Nations chief warned Friday that Ebola may be easing in part of West Africa but is still hitting hard in other areas and outpacing the international response.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.