Diagnosis and Management of C. difficile Infection: Treat Symptoms, Not Stool Samples

With the rate of Clostridium difficile (C. difficile) infection (CDI) in US hospitals increasing at an astronomical rate (doubling between 2000 and 2003, and tripling between 2000 and 2005), physicians need to be aware of the changing epidemiology of CDI, effective approaches to diagnosis and management, treating recurrent infections, and new treatment approaches.

At the 2013 Pri-Med East Conference and Exhibition, Daniel Leffler, MD, MS, Assistant Professor of Medicine, Harvard Medical School, presented “C. difficile Infection: Not Just a Hospital Problem Anymore”

Leffler told the audience that, because of the massive increase in CDI, C. difficile-related mortality is also rapidly increasing; there was a 416% increase between 1999 and 2004. Interestingly, in 2004 there were four times as many CDI-related deaths as there were deaths due to MRSA (methicillin-resistant staphylococcus aureus) infection. In fact, CDI-related deaths were six times higher than all other intestinal infections combined.

The increased mortality is due to increasing incidence and new high-virulence strains (eg, BI/NAP1/027). Leffler said that community-acquired CDI used to be rare, but has seen a 20-fold increase in the past 15 years. In fact, 10-30% of CDI is now community acquired.

Risk factors for CDI include: high-risk antibiotics (4-20-fold increased risk), low-risk antibiotic (2-8-fold increased risk), proton pump inhibitors (2-fold increased risk), and H2-antagonists (1.5-fold increased risk). Other risks include inflammatory bowel disease and advanced age. The signs and symptoms associated with a clinical diagnosis for CDI include diarrhea, abdominal discomfort, nausea, and fever. There are also stool tests for the C. difficile toxin.

According to Leffler, some people have an effective anti-toxin response and become asymptomatic C. difficile carriers, including 50-60% of infants (perhaps due to lack of toxin receptors?), 30% hospitalized and long-term care patients (possibly stemming from high titer serum antitoxin?), and <3% healthy adults (due to barrier function of microflora?).

Leffler’s main advice to clinicians was: “Don’t treat people who are feeling well” and “Treat symptoms not stool samples.” He said bacteria are in the environment and many patients are exposed but do not develop a clinical infection unless the intestinal flora are perturbed. In fact, even when colonized, the patient may have no symptoms—it depends on the immune response of the individual. He advised monitoring the patient as they can get better on their own, and basically to factor in how the patient feels. Additional treatment advice included avoiding anti-diarrheal medications as they can cause toxins to build up.

However, Leffler cautioned that even if patients seem to be doing well, they can get very sick very quickly. Options then are hospitalization and antibiotics. Treatment recommendations for these patients include either metronidazole or vancomycin for mild cases, but vancomycin for severe cases as it is more effective. Leffler reminded the audience that there is no antibiotic resistance so far to these two drugs.

Recurrent C. difficile infection can be treated with a “stool transplant” (fecalmicrobiota transplantation), with healthy human donors donating stool just as they would donate blood. With this approach, patients often recover immediately; Leffler said that one open trial showed a cure in 60 out of 67 patients. Emerging therapies being studied for CDI include non-antibiotic treatment such as toxin binders (eg, tolevamer) and a C. difficile vaccination.