C.diff
Maria G. Tanzi, PharmD
Two new sets of guidelines on the management of Clostridioides difficile are now available—one from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), and the other from the American College of Gastroenterology (ACG).
IDSA/SHEA recommends fidaxomicin (Dificid—Merck) as the preferred agent over vancomycin for an initial episode of C. difficile infection and for an initial recurrence, whereas ACG recommends either fidaxomicin or vancomycin as an option for initial non-severe infection and gives a strong recommendation to use tapered/pulsed dosing of vancomycin for those with an initial recurrence.
“We are using vancomycin as our first-line agent for patients with an initial occurrence of C. difficile, as the cost of fidaxomicin is a real consideration for its use,” said Christopher A. Schriever, PharmD, an infectious diseases specialist and clinical associate professor at the University of Illinois. “Although there may be a potential for less recurrence of C. difficile with use of fidaxomicin as compared with vancomycin, the data are just not that clear yet if this is really the case.”
Vancomycin or fidaxomicin as an initial choice?
Fidaxomicin is listed as the preferred agent by IDSA/SHEA for both initial and recurrent episodes of C. difficile, with oral vancomycin listed as an alternative. Both organizations note that this recommendation places a high value on the beneficial effects and safety of the drug. They do acknowledge, however, that implementation of such a recommendation will depend on the available resources, and that vancomycin remains an acceptable alternative.
To support this recommendation, IDSA/SHEA said that several characteristics of fidaxomicin make it an attractive therapy to treat C. difficile. There are rare reports of resistance to this agent, no other treatment indications, a narrow spectrum, and it has the potential for an improved clinical response (with recurrences being fewer following treatment with fidaxomicin).
ACG, on the other hand, recommends that both vancomycin and fidaxomicin are appropriate initial first-line agents for the management of non-severe infections based upon their review of the available data. They do acknowledge that vancomycin is much less expensive, but the lower recurrence rates of fidaxomicin may imply overall cost-effectiveness of both agents.
Clinicians can also consider an oral course of metronidazole for the treatment of an initial non-severe C. difficile episode in low-risk patients. Both IDSA/SHEA and ACG comment on metronidazole as a potential alternative, with IDSA/SHEA stating it can be used when fidaxomicin or vancomycin are not available.
Clinical applicability of bezlotoxumab, FMT
Use of bezlotoxumab (Zinplava—Merck) is mentioned in both sets of guidelines, with IDSA/SHEA suggesting that this agent can be used in combination with standard-of-care antibiotics for those with a recurrent C. difficile episodes within the last 6 months. They note that bezlotoxumab may be particularly beneficial for patients with a primary episode of
C. difficile and other risk factors for recurrence, including being older than 65 and/or immunocompromised. ACG also states that bezlotoxumab should be reserved for those who are at high-risk of C. difficile recurrence.
“Use of bezlotoxumab should be considered in select patients, as this monoclonal antibody is an infusion and not as easily administered as our current oral regimens,” Schriever said.
Both guidelines also include a discussion on fecal microbial transplantation, with ACG placing a greater emphasis on its use.