1. Clinical Presentation and Initial Assessment

Accurate diagnosis begins with recognizing CDI in at-risk patients presenting with acute-onset diarrhea and systemic signs. Clinical suspicion is rooted in stool frequency and relevant risk factors.

Key Diagnostic Criteria

• Definition of Diarrhea: The presence of three or more unformed stools in a 24-hour period.
• Primary Risk Factors: Recent or current antibiotic use, hospitalization or long-term care residency, age greater than 65 years, and immunosuppression (e.g., from chemotherapy).
• Other Contributing Factors: Use of proton-pump inhibitors, history of prior CDI, and prolonged hospital stays.

Common Signs and Symptoms

• Gastrointestinal: Watery diarrhea (often non-bloody), crampy abdominal pain, bloating, and anorexia.
• Systemic: Low-grade fever, leukocytosis (elevated white blood cell count), tachycardia, and in severe cases, hypotension or altered mental status.
• Fulminant Presentation: Be aware that in cases of ileus (paralysis of the bowel) or toxic megacolon, diarrhea may be absent, masking the underlying infection. A high index of suspicion is required in these critically ill patients.

2. Laboratory Testing Modalities

A multi-step laboratory algorithm is recommended to balance sensitivity and specificity, which helps distinguish active, toxin-producing disease from asymptomatic carriage.

Testing Components

• Screening Assays (High Sensitivity):
  • Glutamate Dehydrogenase (GDH) EIA: Detects a common C. difficile antigen. Sensitivity is >95%, but it does not confirm toxin production and can be positive in colonized patients.
  • Nucleic Acid Amplification Test (NAAT/PCR): Detects the genes for toxins A and/or B. Sensitivity is >90%, but it cannot differentiate between active toxin production and the mere presence of a toxigenic strain.
• Confirmatory Assay (High Specificity):
  • Toxin A/B EIA: Directly detects the presence of active toxins A and B in the stool, confirming active disease. Specificity is >95%, but sensitivity is lower (70–80%), leading to potential false negatives.

3. Imaging and Endoscopic Evaluation

Imaging and endoscopy are not routine for CDI diagnosis but are reserved for patients with severe presentations, suspected complications, or those who fail to respond to initial therapy. Findings can help confirm the diagnosis and direct escalation of care.

Indications for Advanced Evaluation

• Severe abdominal pain, tenderness, or distension.
• Clinical signs of ileus (absent bowel sounds, no passage of stool or gas).
• Signs of systemic toxicity (e.g., shock, high fever) that are refractory to initial antimicrobial therapy.

Modality-Specific Findings

• CT Abdomen/Pelvis with Contrast: The preferred imaging modality. Key findings include marked colonic wall thickening (>4 mm), mucosal hyperenhancement, pericolonic fat stranding, and the “accordion sign” (oral contrast trapped in thickened haustral folds). It is also crucial for screening for abscess or perforation.
• Plain Abdominal Radiograph: Less sensitive than CT but useful for rapidly assessing for toxic megacolon (transverse colon diameter >6 cm) or signs of bowel obstruction like air-fluid levels. “Thumbprinting” due to mucosal edema may also be visible.
• Endoscopy (Flexible Sigmoidoscopy): Reserved for cases where stool testing is impossible (e.g., complete ileus) or results are inconclusive despite high clinical suspicion. The visualization of pathognomonic pseudomembranes—adherent yellow-white plaques on an inflamed mucosal background—confirms the diagnosis. The risk of perforation must be weighed in unstable patients.

4. Severity Stratification Criteria

Classifying CDI severity using objective clinical and laboratory criteria is essential for guiding antimicrobial selection, determining the appropriate level of care, and identifying the need for early surgical consultation.

Treatment Implications based on Severity

• Nonsevere: Defined by WBC ≤15,000 AND Creatinine <1.5. Treat with oral fidaxomicin (200 mg BID) or oral vancomycin (125 mg QID) for 10 days.
• Severe: Defined by either WBC >15,000 OR Creatinine ≥1.5. Treat with the same regimen as nonsevere, but requires inpatient admission and closer monitoring. Adjunct markers like lactate >2 mmol/L or albumin <3 g/dL further support a severe classification.
• Fulminant: Meets severe criteria PLUS the presence of hypotension/shock, ileus, or toxic megacolon. This is a medical emergency requiring ICU admission, high-dose oral/rectal vancomycin (500 mg QID) plus IV metronidazole (500 mg q8h), and an immediate surgical consultation.

5. Clinical Decision Points

Effective management of CDI requires integrating clinical, laboratory, and imaging data to make timely decisions regarding testing, empiric therapy, and escalation of care.

Key Management Principles

• Testing Strategy: Test only symptomatic patients (≥3 unformed stools/24h) with risk factors. Avoid repeat testing within 7 days of starting treatment unless the patient is clinically worsening.
• Empiric Therapy: In patients presenting with severe or fulminant features, initiate empiric antimicrobial therapy immediately while awaiting diagnostic results to prevent clinical deterioration.
• Escalation Criteria: Monitor for signs of worsening, such as a rising WBC count, rising creatinine, increasing lactate, new-onset hemodynamic instability, or imaging findings of megacolon or ileus. These are triggers to escalate care.
• Surgical Consultation: A surgical consult should be obtained early for any patient with fulminant CDI, especially those with toxic megacolon, suspected perforation, or refractory shock despite medical management.