Spore wars: C. diff rise tied to drug resistance

Will U.S. hospitals ban fluoroquinolones?

In its spore form, C. diff is perfectly adapted for dispersal on hands and surfaces, where it can survive for prolonged periods in patient rooms and on medical equipment unless physically removed or killed by powerful solutions like bleach. Moreover, the epidemic NAP1 strain appears to have some capacity for increased spore formation, which gives it a selective advantage in transmitting from hands and surfaces.

"The spores are very hardy and infectious," said L. Clifford McDonald, MD, FACP, a leading C. diff expert in the CDC's division of healthcare quality promotion. "They are ingested by patients presumably from the hands of health care workers who transmit them. The spores are passed into the stomach, where they are relatively stomach-acid resistant and then germinate in the upper intestine. It's really only the person with an altered lower intestinal flora who becomes colonized or infected — [often] someone who has taken antibiotics. That opens up some ecological niche for the C. diff to colonize and cause infection. "

Indeed, emerging C. diff resistance to fluoroquinolones — antibiotics not even used to treat the pathogen — are apparently one key to the NAP1 strain's emergence.

"This strain has been in data bases dating back in the early 1980s, but it was not epidemic until recently," McDonald said. "It became epidemic coincident with it becoming more resistant to the fluoroquinolone antibiotics. The fluoroquinolones are not used to treat C. diff, but they are very popular in our hospitals because they are very potent and have low side-effect profiles. It is thought a strain that had a high level of resistance to these commonly used antibiotics would have a selective advantage over other strains. That seems to be true."

In Europe, successful eradication of C. diff has been driven in large part by intensive infection prevention efforts and strict antibiotic controls, a move that may prove difficult in the U.S. since fluoroquinolones are so widely used for so many infections. An outbreak in the Netherlands, for example, was halted by a complete ban on fluoroquinolone use.

"Somebody in the United States has got to have the guts to do this in hospitals," said Dale Gerding, MD, associate chief of staff for research at the Hines VA Hospital and professor of medicine at Loyola University of Chicago. "I think this is going to be absolutely critical."

The reasons for the U.S. epidemic come further into focus when you complete the aforementioned evolutionary advantages of NAP1 with the final jagged piece of the puzzle: increased virulence.

"The strain is clearly more virulent — we see this in higher severe disease rates and in the epidemiological data," McDonald said. "We know in vitro [it produces] more toxin A and B, which are the main virulence factors. It also produces another binary toxin, but we don't really know what the role of that extra toxin is. There are some reports of changes in the toxin-binding domain and increased sporation. There is good reason to believe this strain is in every state in the continental U.S, and I think we have found it in both Hawaii and Alaska as well."