Clostridioides difficile Management for the Gastroenterologist: Practical Points

Clostridioides difficile bacteria
Illustration of the bacteria Clostridioides difficile. These rod shaped bacteria have flagella, which are used for motility. Clostridioides difficile (formerly known as Clostridium difficile) are anaerobic bacteria prevalent in soil. In humans, the bacteria can become established in the colon and disrupt the normal gut microbiota, particularly in people taking antibiotics. Toxins released by Clostridioides difficile can produce diarrhoea and inflammation.
Up to 40% of Clostridioides difficile infections are community-associated in patients without any significant risk factors such as recent antibiotics, hospitalization, advanced age, inflammatory bowel disease, or history of malignancy.

Clostridioides difficile infection (CDI) is increasingly common in both healthcare and community settings1,2. Up to 40% of CDIs are community associated in patients without any significant risk factors such as recent antibiotics, hospitalization, advanced age, inflammatory bowel disease, or history of malignancy2. Patients with CDI can present with multiple episodes of nonbloody, watery diarrhea that is extra foul-smelling, crampy abdominal pain, and possible fevers.

There have been multiple changes to several CDI guidelines in the last several years, which at this time are still not being followed in certain clinical settings. Recently, Saha et al published a brief review of these changes that are especially applicable to gastroenterologists.3

Many of the changes made to CDI classification management come from the 2017 update of the Infectious Diseases Society of America (IDSA) guidelines, published in 2018.4 One of the major changes in recommendations from this update is to the CDI classification system. The prior 2010 guidelines had a more complicated classification system that was often challenging to remember. Therefore, these updated IDSA guidelines looked to simplify this system.

When evaluating a patient with CDI, it is important to use the most up-to-date nomenclature to stay consistent. On the basis of these guidelines, patients with a CDI episode should be classified as initial, first recurrence, or second subsequent recurrence. Severe disease includes those patients with white blood cell count >15,000 × 106/L, creatinine rise >1.5 times baseline, or creatinine >1.5 mg/dL. Fulminant disease includes patients with hypotension, sepsis, shock, intensive care unit admission, perforation, megacolon, or colectomy. The IDSA guidelines refer to all other cases as nonsevere.

When a patient is diagnosed with CDI in a hospital, it is imperative that the patient be isolated and the appropriate infection control steps be followed until hospital discharge. Those patients in the community should be directed to use thorough hand washing, avoid contact with patients with increased risk of developing CDI, and ideally use their own isolated bathroom in their residence (which needs to be frequently cleaned with bleach-containing products). Consideration of stopping unnecessary antibiotics and acid suppressive medications such as proton pump inhibitors should be taken, as these could predispose patients to severe disease and recurrence.3

Previous guidelines had recommended metronidazole as a first-line agent for the initial episode of CDI. The updated 2017 IDSA guidelines no longer recommend metronidazole as a first-line agent, based on multiple factors. Cumulative dosing can lead to potential neuropathy, as the medication is almost completely absorbed in the small bowel.5 Also, metronidazole only kills the vegetative form of CD, and not the spores, which could predispose a patient to recurrence. However, in scenarios in which other medications are not available or are too expensive, metronidazole can be considered. 

Vancomycin should only be used in its oral formulation for CDI, and not via the intravenous route. It also primarily kills the vegetative form and not the spores. Fidaxomicin (FDX) kills the vegetative form as well as binds the spores to prevent further germination. Rifaximin is recommended by the IDSA 2017 guidelines to only be used as a “chaser” after vancomycin in patients with recurrent CDI (rCDI).4

A key change in the 2017 IDSA guidelines includes first-line agents. Patients with an initial severe or nonsevere CDI episode should receive oral vancomycin 125 mg 4 times daily or FDX 200 mg twice daily for 10 days. Patients with their first recurrence are recommended to be treated with either of the 2 preceding regimens or a tapered and pulsed vancomycin regimen. Second or subsequent recurrences are recommended to be treated with tapered and pulsed vancomycin, FDX, fecal microbiota transplantation (FMT), or vancomycin, followed by a rifaximin chaser. An example of the tapered and pulsed vancomycin regimen includes 125 mg 4 times daily for 10 to 14 days, 125 mg twice daily for 7 days, 125 mg daily for 1 week, and then 125 mg every 2 to 3 days for 2 to 8 weeks.

A key point to consider when comparing FDX and vancomycin for rCDI is that although FDX has been shown to have lower recurrence rates (19.7% vs 35.5%) at 4 weeks posttreatment, there is no difference in recurrence in those patients infected with the NAP1 strain.5,6 Also, both medications can be relatively expensive, and not all pharmacies may have the resources to compound the oral formulation of vancomycin. There is, however, a new, branded version of oral vancomycin; once again, though, the cost could preclude routine patient access.

FMT can be considered in rCDI; however, it may also have limited availability. The CDI cure rates are typically >80% and increase with multiple treatments. FMT can be delivered via upper endoscopy, nasogastric/jejunal tube, capsules, colonoscopy, or enema. In addition, data have shown that fresh and frozen preparations have similar outcomes. Cost can also be an issue with FMT, as many insurances may not provide coverage. In addition to potentially limited access, there is also an occasional negative social stigma toward FMT. Future studies will help further characterize the efficacy and safety data. The FDA is currently gathering both public and medical opinion on FMT, and could provide an updated guidance soon.

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Prevention of rCDI is a popular area of research, with several options available. Bezlotoxumab is an IV infusion of a monoclonal antibody against toxin B that is approved by the US Food and Drug Administration for prevention of rCDI in patients with high risk for recurrence. Oral vancomycin as part of a secondary prophylaxis regimen in patients at risk for rCDI who require antibiotic treatment has accumulating data to support its use. Several vaccines are being studied in clinical trials; however, none is commercially available. Probiotics have limited data in both primary and secondary prevention of CDI; therefore, routine use for these indications is typically not recommended.

CDI and the gut microbiome promise to be some of the most researched topics both now and in the future. Hopefully, future studies will continue to provide data that assist in reducing the significant healthcare effect of CDI.


1. Magill SS, O’Leary E, Janelle SJ, et al. Changes in prevalence of health-care associated infections in US hospitals. N Engl J Med. 2018;379:1732-1744. 

2. Khanna S, Pardi DS, Aronson SL, et al. The epidemiology of community-acquired clostridium difficile infection: a population-based study. Am J Gastroenterol. 2012;107:89-95.

3. Saha S, Khanna S. Management of Clostridioides difficile colitis: insights for the gastroenterologist. Therap Adv Gastroenterol. 2019;6;12:1756284819847651.

4. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):987-994

5. Tannock GW, Munro K, Taylor C, et al. A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile infected patients than does vancomycin. Microbiology. 2010;156:3354-3359.

6. Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55:S154-S161.