What is the workup for Clostridioides difficile (C. diff) colitis?

From the Guidelines

The workup for Clostridioides difficile (C. diff) colitis should begin with stool testing using nucleic acid amplification tests (NAATs) or a two-step algorithm with glutamate dehydrogenase (GDH) antigen followed by toxin testing, as recommended by the most recent guidelines 1. Collect a fresh, unformed stool sample in a clean container and send it to the laboratory promptly. Clinical assessment should include evaluation of symptoms (diarrhea, abdominal pain, fever), recent antibiotic exposure, healthcare facility contact, and immunosuppression status. Laboratory tests should include complete blood count to check for leukocytosis, comprehensive metabolic panel to assess kidney function, and inflammatory markers like C-reactive protein. In severe cases, abdominal imaging with CT scan may be warranted to evaluate for toxic megacolon or colonic wall thickening. Colonoscopy is generally avoided due to perforation risk but may be considered in specific situations like inflammatory bowel disease. Once diagnosed, severity should be assessed based on white blood cell count, serum creatinine, and hemodynamic stability to guide appropriate treatment, considering the latest recommendations for treatment options such as fidaxomicin, vancomycin, and fecal microbiota transplantation 1. Key considerations in the management of C. diff colitis include the potential for recurrence and the need for tailored treatment approaches based on the severity of the disease and the patient's underlying health status, with fecal microbiota transplantation being recommended for patients with multiple recurrences who have failed appropriate antibiotic treatments 1. This comprehensive approach ensures proper diagnosis and management of C. diff colitis, which is crucial as it's a leading cause of healthcare-associated infections with significant morbidity and mortality if not promptly identified and treated. Some studies have explored various treatment options, including vancomycin and metronidazole 1, but the most recent and highest-quality evidence supports the use of fidaxomicin and fecal microbiota transplantation in specific cases 1. The workup and treatment should always prioritize reducing morbidity, mortality, and improving the quality of life for patients with C. diff colitis.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD). 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The workup for C. diff colitis is not explicitly stated in the provided drug labels. However, it can be inferred that diagnosis should involve:

• Culture and susceptibility information, when available
• Consideration of local epidemiology and susceptibility patterns in the absence of culture and susceptibility data
• A strong suspicion of C. difficile infection based on clinical presentation 2 It is essential to note that the provided drug labels focus on the treatment of C. difficile-associated diarrhea rather than the workup for C. diff colitis.

From the Research

Workup for Clostridioides difficile (C. diff) Colitis

The workup for C. diff colitis involves a combination of physical examination, laboratory tests, radiographic evaluation, and endoscopic evaluation.

• A focused history and physical examination will help guide initial management 3.
• Laboratory testing includes stool studies, such as:
  • Enzyme immunoassay (EIA) for toxin A and B detection, which has a sensitivity of 60-70% and specificity of 98% 4.
  • Real-time PCR methods, which detect the gene coding for toxin B and can also detect toxin A-negative, toxin B-positive strains 5.
  • Nucleic acid amplification testing (NAAT), which appears to be the most efficient study to detect the gene that encodes for toxin A and B 6.
• Blood tests, such as white blood cell counts and serum creatinine, can help stratify patients into illness severity groups for treatment decisions 3.
• Radiographic evaluation can be helpful in patients with severe disease and concern for complicated colitis 3.
• Endoscopic evaluation should be carefully considered in patients with suspected mucosal injury secondary to infections and plays a role when an alternative diagnosis is suspected 3, 6.

Diagnostic Algorithm

A two-step algorithm for detection of toxigenic C. difficile in stool has been proposed, which includes initial screening for glutamate dehydrogenase assay followed by confirmation by toxin A+B detection using an EIA or molecular assay 7, 4.

• The GeneXpert C. difficile polymerase chain reaction (PCR) assay can be used as a reference standard to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of other diagnostic tests 7.
• Toxigenic culture has emerged as the new gold standard against which newer assays should be compared, but there is no agreed upon standard method for culture performance 4.

Special Considerations

• Infants have a high carriage rate of C. diff and are believed not to develop disease from it or its toxins, and therefore should not be tested for C. difficile 6.
• Testing for C. difficile should only be done on patients with diarrhea, as the presence of toxin-producing strains of C. diff in the stool does not equate with disease 6.