Product Review

New Treatment for C. difficile Infection

Often considered a hospital-associated illness, Clostridium difficile (C. difficile) infection (CDI) also occurs in nursing homes and within the community. This sometimes-fatal bacterial infection impedes virtually all aspects of sufferers’ lives and keeps them bound to home or hospital. With growing rates of C. difficile infection-related mortality in the presence of hyper-virulent (severe and more toxic) strains, a combination of effective preventative measures and appropriate frontline treatments for those who do become infected is essential. Although it has been more than twenty years since a new agent emerged to treat CDI, Health Canada recently approved an encouraging new antibiotic therapy, fidaxomicin (Dificid™).

Our guts contain a unique microbiome consisting of a vast diversity of good microorganisms and small amounts of microorganisms that cause disease in the host (pathogenic). Fewer than 5% of the general population have small colonies of the pathogenic C. difficile bacterium in their digestive tracts, but this alone does not cause illness. A robust collection of good intestinal microorganisms in the gut keeps small populations of C. difficile in check. Infectionoccurs when this bacterium overpopulates within the gut due to a disruption of the microbiome. Several antibiotics that are good at treating bacterial infections have the side effect of also killing the good bacteria normally residing in the gut, resulting in an imbalance in the microbiome and allowing for overgrowth of pathogenic bacteria.

C. difficile produces specific toxins that can damage the bowel and cause watery diarrhea, fever, abdominal pain, and cramping. Individuals with weakened immune or digestive systems (e.g., the elderly and those with severe digestive conditions) and/or those who have been taking broad-spectrum antibiotics for other illnesses are especially vulnerable to microbiome disruptions. They are also at a higher risk for C. difficile and related complications. One of the most significant issues for patients suffering from CDIis that it can come back multiple times – about 25% of patients will suffer at least one relapse and this risk increases with each additional infection.

C. difficile spores spread through the environment and contaminate surfaces in washrooms, hallways, and on bedrails, etc., potentially re-infecting a patient who has already received one successful antibiotic treatment and infecting others. The spores can survive for months on surfaces and are resistant to gastric acid, antibacterial soaps, and alcohol-based hand sanitizers. Good hand washing techniques, using soap and warm water, are effective in preventing the spread of C. difficile, but social monitoring of hand washing is problematic.Diarrhea associated with C. difficile is often explosive and uncontrollable, which worsens its infectious component.

So how could an antibiotic be effective against an illness caused by antibiotics? Dificid, a breakthrough treatment option, is a very narrow-spectrum antibiotic that works by killing C. difficile in the gut, suppressing the production of certain C. difficile toxins, and inhibiting the production of spores, while preserving the normal gut microbiome.

There are two main antibiotics that physicians have been using to treat C. difficile infection, metronidazole and vancomycin. Metronidazole circulates through the entire body when taken and has limited effectiveness against more severe disease, and its side effects may preclude long-term use. Dificid stays in the gut and is only minimally absorbed in the rest of the body. Although vancomycin is targeted to the gut, its extensive use has lead to some C. difficile strains becoming resistant, especially if a patient has been repeatedly re-infected.

Two international clinical trials, which included more than 400 Canadian patients, showed that about 15% of patients on Dificid experienced a recurrence of infection, compared to 25% of those given vancomycin. A decreased recurrence rate comes at a price; $2,200 for a 10 day course of Dificid (200mg twice daily), compared to $400 for a 10 day course of vancomycin (125mg four times daily). The overall rate of side effects assigned by the clinical investigators as being possibly or definitely related to Dificid in Phase 3 clinical trials was 10.6% (equivalent to vancomycin); the most common were nausea (2.7%), constipation (1.2%), and vomiting (1.2%).

Since almost all antibiotics can increase a person’s risk for C. difficile infection, an emphasis on antibiotic stewardship is important. Use of Dificid, a targeted antibiotic that research has shown to be safe and effective, is part of this stewardship.

First published in the Inside Tract® newsletter issue 184 – 2012
Note: The GI Society has received no remuneration from Dificid™ or its affiliates for this review.