Clostridioides (Clostridium) Difficile Colitis Guidelines

Updated: Jul 25, 2019
  • Author: Faten N Aberra, MD, MSCE; Chief Editor: BS Anand, MD  more...
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ISDA and SHEA Guidelines on CDI

The following recommendations on Clostridium difficile infection (CDI) were released in February 2018 by the Infectious Diseases Society of America (ISDA) and Society for Healthcare Epidemiology of America (SHEA). [46, 47]

Diagnosis (adults)

Patients with unexplained and new-onset ≥3 unformed stools in 24 hours are the preferred target population for testing for CDI.

Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than NAAT alone for all specimens when there are no preagreed institutional criteria for patient stool submission.

Use NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission.

Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiologic studies.

Diagnosis (pediatric)

Because of the high prevalence of asymptomatic carriage of toxigenic C difficile in infants, testing for CDI should never be routinely recommended for neonates or infants ≤12 months of age with diarrhea.

C difficile testing should not be routinely performed in children with diarrhea who are 1-2 years of age unless other infectious or noninfectious causes have been excluded.

In children ≥2 years of age, C difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (eg, underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (eg, contact with the healthcare system or recent antibiotics).

Treatment (adults)

Discontinue therapy with the inciting antibiotic agent(s) as soon as possible, as this may influence the risk of CDI recurrence.

Antibiotic therapy for CDI should be started empirically for situations where a substantial delay in laboratory confirmation is expected, or for fulminant CDI.

Either vancomycin or fidaxomicin is recommended over metronidazole for an initial episode of CDI. The dosage is vancomycin 125 mg orally 4 times per day or fidaxomicin 200 mg twice daily for 10 days.

In settings where access to vancomycin or fidaxomicin is limited, metronidazole is suggested for an initial episode of nonsevere CDI only. The suggested dosage is metronidazole 500 mg orally 3 times per day for 10 days. Avoid repeated or prolonged courses due to the risk of cumulative and potentially irreversible neurotoxicity.

For fulminant CDI, vancomycin administered orally is the regimen of choice. If ileus is present, vancomycin can also be administered per rectum. The vancomycin dosage is 500 mg orally 4 times per day and 500 mg in approximately 100 mL normal saline per rectum every 6 hours as a retention enema. Intravenously administered metronidazole should be administered together with oral or rectal vancomycin, particularly if ileus is present. The metronidazole dosage is 500 mg intravenously every 8 hours.

If surgical management is necessary for severely ill patients, perform subtotal colectomy with preservation of the rectum. Diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes is an alternative approach that may lead to improved outcomes.

Treat a first recurrence of CDI with oral vancomycin as a tapered and pulsed regimen rather than a second standard 10-day course of vancomycin; OR treat a first recurrence of CDI with a 10-day course of fidaxomicin rather than a standard 10-day course of vancomycin; OR treat a first recurrence of CDI with a standard 10-day course of vancomycin rather than a second course of metronidazole if metronidazole was used for the primary episode.

Fecal microbiota transplantation is recommended for patients with multiple recurrences of CDI whose conditions have failed appropriate antibiotic treatments.

Treatment (pediatric)

Either metronidazole or vancomycin is recommended for the treatment of children with an initial episode or first recurrence of nonsevere CDI.

For children with an initial episode of severe CDI or with a second or greater episode of recurrent CDI, oral vancomycin is recommended over metronidazole.


WSES Guidelines on CDI

The World Society of Emergency Surgery (WSES) released guidelines on diagnosis and treatment of Clostridioides (Clostridium) difficile infection (CDI) in surgical patients in February  2019. [69]


Diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests. Stool testing should only be performed on diarrheal stools from at-risk patients with clinically significant diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation.

For patients with ileus who may be unable to produce stool specimens, polymerase chain reaction (PCR) testing of perirectal swabs is an acceptable alternative to stool specimen analysis.

Nucleic acid amplification testing (NAAT) for C difficile toxin genes appears to be sensitive and specific and may be used as a standard diagnostic test for CDI. NAAT may be performed as a single-step algorithm or included in a two-step algorithm starting with toxin enzyme immunoassay (EIA).

Glutamate dehydrogenase (GDH) testing is sensitive but does not differentiate between toxigenic and nontoxigenic strains. It may be used in association with toxin A/B EIA testing. Algorithms including screening with EIA for GDH followed by toxin assay may be suggested.

EIA for toxin A/B is fast, inexpensive, and highly specific but is relatively insensitive and is not recommended alone.

C difficile culture is relatively slow but sensitive and is rarely performed as a routine diagnostic test. It is recommended for subsequent epidemiologic typing and characterization of strains.

Repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with (a) ongoing clinical suspicion during an epidemic situation or (b) high clinical suspicion during endemic situations.

Computed tomography (CT) is suggested for patients with clinical manifestations of severe-to-complicated C difficile colitis; however, it is not sensitive enough for screening.

Ultrasonography (US) may be useful in critically ill patients suspected of having pseudomembranous colitis who cannot be transported to the CT suite.

Flexible sigmoidoscopy may be helpful in diagnosing C difficile colitis when there is a high level of clinical suspicion for CDI.

Antibiotic therapy

Unnecessary antibiotics should be discontinued if CDI is suspected. Unnecessary proton pump inhibitors (PPIs) should be discontinued in patients at high risk for CDI.

Empirical antibiotic therapy should be avoided unless CDI is strongly suspected. In such cases, empirical therapy for CDI should be considered while test results are awaited.

Oral metronidazole should be limited to treatment of an initial episode of mild-to-moderate CDI. Oral vancomycin is recommended for treatment of mild-to-moderate disease unresponsive to metronidazole. Repeated or prolonged courses of metronidazole should be avoided. Oral vancomycin and fidaxomicin are both recommended for treatment of severe CDI.

When oral antibiotics cannot reach the colon, vancomycin may be administered as a retention enema via a large rectal tube or catheter.

Fidaxomicin may be used to treat CDI, especially in patients at higher risk for recurrence (eg, elderly patients or those receiving concomitant antibiotics).

Surgical management

Patients with severe CDI who progress to systemic toxicity should undergo early surgical consultation and should be evaluated for potential surgical intervention.

For patients with fulminant colitis, total colectomy should be considered. However, diverting loop ileostomy with colonic lavage is a useful alternative.

Fulminant colitis should be treated with high-dose vancomycin (500 mg q6hr), orally or via enema or both, in combination with intravenous (IV) metronidazole (500 mg q8hr).

Supportive care

Early detection of shock and aggressive management of organ dysfunction are essential for improved outcomes in fulminant colitis. Supportive measures (eg, IV fluid resuscitation, albumin supplementation, and electrolyte replacement) should be provided to all patients with severe CDI.

Recurrent CDI

The first recurrence of CDI may be treated with vancomycin (particularly if metronidazole was used for the initial episode) or fidaxomicin. Antibiotic options for further recurrences include oral vancomycin in a tapered and pulsed regimen.


Limited direct evidence supports the use of probiotics in managing a first episode of CDI as an adjunct to antibiotics for immunocompetent patients.

Prophylactic probiotics may be considered for inpatients receiving antibiotics during a high-risk period before the disease develops. Probiotics should be not used in immunocompromised patients.

Probiotics for prevention of recurrent CDI may be an effective adjunct to standard antibiotic treatment (vancomycin) in patients with at least one prior episode of CDI.

Fecal microbiota transplantation

Fecal microbiota transplantation (FMT) may be an effective option for patients with multiple recurrences of CDI in whom appropriate antibiotic treatments have failed.

Monoclonal antibodies

Coadjuvant monoclonal antibody (bezlotoxumab) therapy may prevent CDI recurrences, particularly in patients who have CDI due to the 027 epidemic strain, are immunocompromised, or have severe CDI.

Intravenous immunoglobulin

IV immunoglobulin (IVIG) should be used only as adjunctive therapy in patients with multiple recurrences or fulminant CDI.

Enteral nutrition

Tube feeding patients should be clinically assessed due to their risk for developing CDI.

Antimotility agents

The use of antiperistaltic agents to treat CDI is discouraged. If such agents are used to control persistent symptoms, they must always be accompanied by medical therapy.


BSG and HIS Guidelines on FMT

2018 BSG and HIS guidelines on FMT

In September 2018, the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) released guidelines on best practices of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile infection (CDI) and for potential non-CDI indications in adults. [70]

FMT should be offered to patients with CDI who have had at least 2 recurrences and to patients who have had one recurrence and also have risk factors for additional recurrences.

Consider FMT in cases of refractory CDI.

Do not administer FMT as the initial treatment for CDI.

Recommend that FMT be considered for recurrent CDI only after recurrence following resolution of an episode of CDI treated with appropriate antimicrobials for at least 10 days.

Recommend considering extended/pulsed vancomycin and/or fidaxomicin before FMT is considered for recurrent CDI.

In cases of severe or complicated CDI, before offering FMT, recommend considering treatment with medications such as fidaxomicin and bezlotoxumab, which are associated with reduced risk of recurrence.

Recommend that FMT be offered after initial failure of FMT.

Clinicians should follow-up FMT recipients for at least 8 weeks in total.

Recommend that patients be warned about short-term adverse effects of FMT, particularly possible self-limiting GI symptoms, and be advised that serious adverse effects are rare.

Recommend that, after enteral tube administration, the tube be removed and oral water given following 30 minutes after tube administration.

Recommend that FMT be avoided in patients who have anaphylactic food allergy.

Suggest that FMT be offered with caution to patients who have CDI and decompensated chronic liver disease.

Recommend that FMT be offered with caution to immunosuppressed patients, in whom FMT appears to be efficacious without significant additional adverse effects.

Recommend that patients who are immunosuppressed and at risk of severe infection if exposed to Epstein–Barr virus (EBV) or cytomegalovirus (CMV) receive FMT only from donors who are negative for Epstein-Barr virus (EBV) and cytomegalovirus (CMV).

Suggest that people be considered as potential FMT donors only if they are 18 to 60 years of age and have a body mass index of 18 to 30 kg/m2.