What is the diagnosis and management of a patient with severe Clostridioides difficile (C. diff) infection?

From the Guidelines

Severe Clostridioides difficile infection should be managed with oral vancomycin 500 mg four times daily, as it is the most effective treatment for severe cases, particularly those with hypotension, shock, ileus, or megacolon, as recommended by the most recent guidelines 1.

Diagnosis

Severe Clostridioides difficile infection is diagnosed based on clinical presentation of severe diarrhea (>3 loose stools per day), abdominal pain, fever, and laboratory findings including positive C. difficile toxin assay, elevated white blood cell count (>15,000 cells/μL), and elevated serum creatinine (>1.5 times baseline) 1.

Management

Management of severe C. difficile infection should begin with oral vancomycin 500 mg four times daily for 10 days, as it is considered superior to metronidazole in severe CDI 1. For cases with ileus, vancomycin enemas (500 mg in 100 mL normal saline every 6 hours) may be added to the treatment regimen 1. Fidaxomicin 200 mg twice daily for 10 days is an alternative with lower recurrence rates, particularly useful for treating patients who are considered at high risk for recurrence 1. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, may be administered as a single infusion to prevent recurrence in high-risk patients 1.

Supportive Care

Supportive care includes fluid resuscitation, electrolyte replacement, and avoiding antimotility agents. Surgical consultation for possible colectomy is necessary if the patient develops toxic megacolon, perforation, or refractory septic shock 1.

Fecal Microbiota Transplantation

Fecal microbiota transplantation (FMT) is an effective option for patients with multiple CDI recurrences who have failed appropriate antibiotic treatments, and may be considered in hospitalized patients with severe or fulminant CDI not responding to antimicrobial therapy 1.

• Key considerations for FMT include:
  • Patient selection: hospitalized patients with severe or fulminant CDI not responding to standard of care antibiotics
  • Donor stool screening: appropriately screened donor stool should be used for FMT
  • Administration: FMT should be performed via colonoscopy or flexible sigmoidoscopy, with follow-up doses administered every 3-5 days as needed
  • Anti-CDI antibiotics: may need to be continued after FMT, with suppressive vancomycin continued at discharge to prevent CDI recurrence 1

From the FDA Drug Label

Enrolled patients were 18 years of age or older and had a confirmed diagnosis of CDI, which was defined as diarrhea (passage of 3 or more loose bowel movements in 24 or fewer hours) and a positive stool test for toxigenic C difficile from a stool sample collected no more than 7 days before study entry. Patients were assessed for clinical cure of the presenting CDI episode, defined as no diarrhea for 2 consecutive days following the completion of a ≤14 day SoC regimen. The following risk factors associated with a high risk of CDI recurrence or CDI-related adverse outcomes were present in the study population: 51% were ≥65 years of age, 39% received one or more systemic antibacterial drugs (during the 12-week follow-up period), 28% had one or more episodes of CDI within the six months prior to the episode under treatment (15% had two or more episodes prior to the episode under treatment), 21% were immunocompromised and 16% presented at study entry with clinically severe CDI (as defined by a Zar score of ≥21).

The diagnosis of a patient with severe C. diff infection is based on the presence of diarrhea (passage of 3 or more loose bowel movements in 24 or fewer hours) and a positive stool test for toxigenic C. difficile. The management of severe C. diff infection involves a 10- to 14-day course of oral Standard of Care (SoC) antibacterial drugs, such as metronidazole, vancomycin, or fidaxomicin, and may include the use of bezlotoxumab (ZINPLAVA) to reduce the risk of recurrence. Key risk factors for CDI recurrence or CDI-related adverse outcomes include age ≥65 years, history of CDI in the past 6 months, immunocompromised state, severe CDI at presentation, or C. difficile ribotype 027 2.

From the Research

Diagnosis of Severe C. Diff

• Severe C. diff infection is typically diagnosed based on a combination of clinical presentation, laboratory tests, and imaging studies 3.
• The diagnosis is often made in patients with severe diarrhea, abdominal pain, and fever, particularly in those with a history of antibiotic use or hospitalization 3.
• Laboratory tests, such as stool tests for C. diff toxins, and imaging studies, such as abdominal CT scans, may be used to confirm the diagnosis and assess the severity of the infection 3.

Management of Severe C. Diff

• The management of severe C. diff infection typically involves a combination of supportive care, antibiotic therapy, and fecal microbiota transplantation (FMT) 4, 5.
• Supportive care measures, such as fluid and electrolyte replacement, may be necessary to manage dehydration and electrolyte imbalances 3.
• Antibiotic therapy, such as vancomycin or fidaxomicin, may be used to treat the infection, but FMT has been shown to be a highly effective treatment option, particularly for recurrent C. diff infection 4, 6.
• FMT involves the transfer of fecal microbiota from a healthy donor into the colon of the patient, and has been shown to be effective in resolving C. diff infection and preventing recurrence 4, 5, 6, 7.

Fecal Microbiota Transplantation (FMT)

• FMT has been shown to be a highly effective treatment option for severe C. diff infection, with success rates ranging from 78% to 93% 4, 5, 6, 7.
• FMT may be performed via colonoscopy, and the procedure is generally well-tolerated with minimal adverse effects 4, 6.
• The use of FMT has been shown to be effective in preventing recurrence of C. diff infection, and may also have a positive impact on underlying inflammatory bowel disease (IBD) outcomes 7.

Special Considerations

• Patients with severe C. diff infection may require hospitalization and close monitoring, particularly if they have underlying medical conditions or are at risk for complications such as toxic megacolon or sepsis 3, 5.
• The use of FMT in patients with IBD has been shown to be effective in preventing recurrent C. diff infection, and may also have a positive impact on IBD outcomes 7.