In an older adult with new‑onset watery diarrhea (≥3 unformed stools in 24 hours), abdominal cramping, fever and leukocytosis, how should suspected Clostridioides difficile infection be diagnosed and managed initially?

Diagnosis and Initial Management of Suspected Clostridioides difficile Infection in Older Adults

In an older adult with new-onset watery diarrhea (≥3 unformed stools in 24 hours), abdominal cramping, fever, and leukocytosis, immediately place the patient on contact precautions, send a single stool sample for a two-step diagnostic algorithm (GDH or NAAT screening followed by toxin confirmation), and initiate oral vancomycin 125 mg four times daily for 10 days as first-line therapy. 1

Immediate Actions Upon Suspicion

Infection Control Measures

• Place the patient on contact precautions immediately while awaiting test results if same-day testing is unavailable 1
• Healthcare personnel must wear gloves and gowns upon room entry and during all patient care 1
• Wash hands with soap and water, not alcohol-based sanitizers, as alcohol does not inactivate C. difficile spores 2

Discontinue Contributing Factors

• Stop the inciting antibiotic immediately if clinically feasible, as continued exposure dramatically increases recurrence risk 1, 2
• Discontinue proton pump inhibitors if possible, as they are associated with increased CDI risk 1
• Do not use antiperistaltic agents (e.g., loperamide), as they can precipitate toxic megacolon and mask disease severity 2, 3

Diagnostic Testing Strategy

Who to Test

• Test only patients with ≥3 unformed stools in 24 hours who are not taking laxatives 1
• The clinical presentation described (watery diarrhea, abdominal cramping, fever, leukocytosis) meets criteria for testing 1, 4
• Do not test asymptomatic patients or those with formed stools, as this detects colonization rather than infection 1, 2, 5

Recommended Testing Algorithm

Use a two-step diagnostic approach for optimal sensitivity and specificity 1:

1. First step: Glutamate dehydrogenase (GDH) antigen test or nucleic acid amplification test (NAAT/PCR) for high sensitivity (91-100%) 1, 2
2. Second step: Toxin A/B enzyme immunoassay for confirmation with high specificity (98-99%) 1, 2

• This multistep algorithm balances sensitivity with specificity and reduces false-positives from asymptomatic colonization 1, 2
• Do not use toxin EIA alone as its sensitivity is only 70-80%, risking missed diagnoses 2
• When institutional criteria ensure appropriate patient selection (≥3 unformed stools, no laxatives), NAAT alone is acceptable 1

Specimen Collection

• Submit a single unformed stool specimen—one sample is sufficient for diagnosis 1, 3
• Do not perform repeat testing within 7 days during the same diarrheal episode 1
• Do not perform "test of cure" after treatment, as patients may shed spores for up to 6 weeks despite clinical resolution 1, 2, 4

Initial Treatment

First-Line Therapy for Initial Episode

Oral vancomycin 125 mg four times daily for 10 days is the recommended first-line treatment for an initial CDI episode, achieving clinical success rates of approximately 81% 1, 2, 6

• Metronidazole is no longer recommended as first-line therapy for adults 1, 2, 7
• Vancomycin is preferred regardless of initial severity classification in current guidelines 2, 7

Assessing Disease Severity

Severe CDI is defined by any of the following 1, 2, 4:

• White blood cell count ≥15,000 cells/mm³
• Serum creatinine >1.5 times baseline (≥133 μmol/L)
• ≥10 unformed stools per day
• Fever >38.5°C
• Hypoalbuminemia <2.5 g/dL

Fulminant CDI includes 2, 4:

• Hypotension or septic shock
• Ileus or toxic megacolon
• Peritoneal signs
• Elevated serum lactate indicating organ failure

Treatment for Severe/Fulminant Disease

For severe disease without complications, continue oral vancomycin 125 mg four times daily for 10 days 2

For fulminant CDI (hypotension, ileus, toxic megacolon) 2:

• Urgent surgical consultation with low threshold for total colectomy
• Combination therapy: Oral vancomycin 500 mg four times daily plus IV metronidazole 500 mg every 8 hours
• If ileus prevents oral medication from reaching the colon, add vancomycin enemas (500 mg in 100 mL saline four times daily)
• Aggressive supportive care with fluid resuscitation and electrolyte monitoring (particularly magnesium and potassium, as deficiencies increase toxic megacolon risk) 4

Common Pitfalls to Avoid

• Testing patients on laxatives or with formed stools—this detects colonization, not infection 1, 2, 4
• Using toxin EIA as the sole diagnostic test—low sensitivity (70-80%) results in missed cases 2
• Continuing the inciting antibiotic—dramatically raises recurrence risk (18-25% baseline recurrence rate) 2, 6
• Prescribing antiperistaltic agents—can precipitate toxic megacolon 2, 3
• Using alcohol-based hand sanitizers alone—ineffective against C. difficile spores; soap and water required 2
• Performing repeat testing within 7 days—leads to false-negatives due to intermittent toxin shedding 1, 2
• Ordering "test of cure" after treatment—56% of successfully treated patients continue shedding spores asymptomatically for weeks 1, 4

Monitoring and Follow-Up

• Clinical improvement (diarrhea resolution, reduced abdominal pain) typically occurs within 3-5 days of starting vancomycin 6, 8
• Monitor complete blood count and serum creatinine in severe cases to assess response 1, 4
• Recurrence occurs in 18-25% of patients within 4 weeks after completing initial therapy 2, 6
• If symptoms persist beyond 5-7 days despite appropriate therapy, consider imaging (CT abdomen/pelvis) to evaluate for complications 2
• Distinguish true recurrence from post-infectious irritable bowel syndrome, which occurs in 4.3% of patients beyond 3 months 1, 4