“While the burden of diarrhea and colitis due to C. difficile infection (CDI) has decreased slightly in the United States, it is still responsible for nearly 500,000 cases, and 70,000 recurrent cases, each year,” explains Stuart Johnson, MD. “Recurrent CDI remains one of the most important treatment challenges for patients and their physicians. Most patients will respond to treatment with either of the two recommended drugs—vancomycin or fidaxomicin—but approximately 20% of patients develop recurrent diarrhea symptoms within 1 or several weeks after completing treatment for the prior episode. The risk for a subsequent recurrence in patients who have already had a recurrence is now approximately 40%.”

Some patients, Dr. Johnson continues, will have multiple recurrences, typically responding to repeated treatments with either vancomycin or fidaxomicin, but predictably developing symptoms again after stopping treatment. “The issue with recurrent CDI is not development of resistance to the drugs, but the failure to restore the natural protective immunity provided by the microbiota in the large intestine,” he adds.

Possible Implementation Barriers

In Clinical Infectious Diseases, Dr. Johnson and colleagues updated the Infectious Disease Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines on the management of CDI in adults.  “Since publication of the last iteration of the guidelines in early 2018, new data have emerged for fidaxomicin and for bezlotoxumab, a monoclonal antibody targeting toxin B produced by CDI,” Dr. Johnson notes. “Both of these agents have increased clinical efficacy and other advantages compared with older agents, but there may be barriers to implementation due to cost and logistics.”

Fidaxomicin is now the preferred treatment for an initial CDI episode and a first recurrent CDI episode, Dr. Johnson and colleagues concurred. “Vancomycin is still an acceptable alternative treatment and it is important to note that the data supporting these recommendations are not as robust for recurrent CDI,” says Dr. Johnson. “There is no ‘preference’ of treatment for patients with multiple recurrences (second or subsequent recurrence), but several options include vancomycin in a tapered and pulsed regimen, fidaxomicin in a standard or extended-pulsed regimen, and fecal microbiota transplantation (FMT). Although FMT has received much emphasis during the last decade—and may be recommended for some patients who have failed to respond to antibiotic treatment—it is still not FDA-approved, there is variability in screening donors, there are some risks, and it is not covered by insurance. Recommendations are also made for bezlotoxumab as adjunctive treatment to be given along with a standard antibiotic treatment (Table).”

 Additional Research Needed

Although the data support an increased role for fidaxomicin and bezlotoxumab in clinical practice, the researchers acknowledge the increased cost and logistical issues involved in getting many patients access to these newer agents. “It is our hope that the guideline update will give impetus to both the pharmaceutical industry and insurance providers to increase availability and access to these agents,” Dr. Johnson says.

The guideline-writing committee emphasizes that additional well-controlled RCTs are needed to help refine these recommendations. Randomized studies are also needed before any recommendations can be made for prophylaxis, Dr. Johnson adds. “While it may seem practical to give vancomycin to patients who have had CDI and who are subsequently put at risk by additional antibiotic treatments, this drug has significant ‘off target’ effects on the protective colonic microbiota and may, paradoxically, put patients at increased risk of CDI.”