The risks for C. diff are generally greater among the patient subgroups more likely to be treated with antibiotics – those with spinal cord injuries, for example, who often undergo invasive procedures or treatments that increase the risk of infection. At the Hines VAMC, where Dr. Charlesnika Evans co-directs the VA’s Spinal Cord Injury Quality Enhancement Research Initiative (SCI-QUERI), studies have shown that antibiotic use is the leading risk factor for the recurrence of a C. diff infection for veteran patients with an SCI.

“So we’re really trying to develop research projects that focus on improving antimicrobial stewardship,” said Evans, “and stewardship can mean several things: It can mean decreasing the use of antibiotics overall. It could be managing patients in a different way, going from more broad-spectrum antibiotics that kill everything – but also promote antibiotic resistance – to moving to more narrow-spectrum antibiotics, which are really focused on a particular type of microorganism.”

In the longer term, the developing knowledge of the human microbiome may offer a significant option for treatment, and perhaps even a cure. A Dutch study of C. diff patients, reported in the New England Journal of Medicine in January 2013, compared two treatments among patients with C. diff-associated diarrhea: One group was treated with both vancomycin and the transplant of donated feces into their bowels; the other groups were treated either with vancomycin alone or with vancomycin and bowel lavage. Among the 16 patients receiving fecal transplants, 15 had resolution of C. diff-associated diarrhea. “They stopped the study early,” said Lockette, “because they felt it was unethical to proceed, given how much more effective the fecal transplants were at relieving C. difficile infection … When you give someone a fecal transplant, you’re giving them a microbiome that presumably has more of the healthy microbes in it and it allows the healthy microbes that are being transplanted to overtake the C. difficile microbes in the ill patient.”

Despite such startling promise, approval of fecal transplants by the Food and Drug Administration (FDA) as a treatment for C. diff isn’t about to happen; investigators can show that it works, but they still have no idea why. “The problem,” Lockette said, “is that you don’t know which bacteria you’re transplanting is the good bacteria, the one that suppresses the C. difficile. When you take a probiotic, you’re taking a specific good bacteria, also, but you don’t know if it’s the right good bacteria that will suppress the C. difficile.”

Equally promising – and closer to FDA approval for clinical use – is Gerding’s research at the Hines VAMC, which has focused on preventing relapse in C. diff patients by displacing the toxigenic organism with a non-toxigenic strain of C. diff that already exists in nature. “They’re out there circulating around, just like the toxin-producing strains are,” he said. “We’ve been able to show in both animal and human models that when patients have these strains in the gut, they don’t get sick with the toxigenic strains.” In a phase 2 clinical trial, Gerding’s team showed that patients who received oral doses of non-toxigenic C. diff – about 10 million spores a day, for a week – were colonized with the harmless strain, blocking a recurrence of the disease in more than 90 percent of the subjects.

Gerding’s procedure is one of the most exciting developments to emerge from the VA’s research program in recent years, and at the beginning of 2014, he was awarded the William S. Middleton Award for outstanding achievement in biomedical research, the highest achievement awarded by the VA’s Biomedical Laboratory Research and Development Service. The procedure has one more hurdle to clear – a phase 3 clinical trial, for final confirmation of safety and efficacy – before it’s eligible for FDA approval, but it’s a treatment that could make toxigenic C. difficile far less threatening to patients receiving medical care.

This article first appeared in The Year in Veterans Affairs & Military Medicine 2014-2015 Edition.