New Guideline for Prevention, Diagnosis, and Treatment of C diff

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).

New Faces Among Familiar Ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.

Special Populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.

Reflecting the Research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Khanna has coauthored previous guidelines on  C. difficile . He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

This article originally appeared on, part of the Medscape Professional Network.

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