What laboratory tests should be ordered to evaluate a patient with diarrhea?

Laboratory Workup for Diarrhea

The laboratory evaluation of diarrhea should be stratified based on whether the presentation is acute or chronic, with acute diarrhea requiring stool testing primarily when fever, bloody/mucoid stools, severe cramping, or signs of sepsis are present, while chronic diarrhea necessitates a broader initial screening followed by targeted testing based on clinical suspicion.

Acute Diarrhea (<14 days)

Initial Assessment

First, evaluate for dehydration in all patients, as this increases mortality risk, especially in young children and elderly adults 1.

When to Order Stool Tests

Stool testing is indicated when patients present with:

• Fever
• Bloody or mucoid stools
• Severe abdominal cramping or tenderness
• Signs of sepsis
• Symptoms lasting >7 days
• Circumstances suggesting infection 1, 2

Specific Stool Tests for Acute Diarrhea

Standard bacterial panel should include:

• Salmonella
• Shigella
• Campylobacter
• Yersinia (especially in children with right lower quadrant pain or exposure to undercooked pork)
• STEC (both O157 and non-O157 serotypes)
• Clostridioides difficile 1

For STEC detection specifically:

• Use sorbitol-MacConkey agar or chromogenic agar for O157:H7
• Detect Shiga toxin or use genomic assays for non-O157 STEC
• If available, distinguish between Shiga toxin 1 and 2 (toxin 2 is more potent) 1

Additional testing based on exposure history:

• Vibrio species: Test when patient has large volume rice-water stools, exposure to brackish water, consumption of raw shellfish, or travel to cholera-endemic regions within 3 days of symptom onset 1
• Enteric fever pathogens (Salmonella Typhi/Paratyphi): Consider in febrile patients with travel to endemic areas or exposure to foods prepared by recent travelers 1

Blood Cultures

Obtain blood cultures when:

• Infant <3 months of age
• Signs of septicemia at any age
• Enteric fever suspected
• Immunocompromised status
• High-risk conditions (e.g., hemolytic anemia)
• Febrile illness of unknown etiology with travel to enteric fever-endemic areas 1

Modern Diagnostic Approaches

PCR-based multiplex panels provide results within 6 hours and demonstrate consistent sensitivity and specificity, making them ideal for rapid diagnosis 2, 3. However, for C. difficile, use a two-step approach: initial highly sensitive test (glutamate dehydrogenase) followed by toxin-specific testing (nucleic acid amplification for toxin B or enzyme immunoassays for toxins A/B) to distinguish infection from colonization 2.

Chronic Diarrhea (>4 weeks)

Initial Screening Tests

Blood tests should include:

• Complete blood count (to exclude anemia)
• Celiac serology (tissue transglutaminase antibodies) - test in ALL patients regardless of stool pattern 4, 5
• Basic metabolic panel
• Inflammatory markers (CRP) 4, 3

Stool tests should include:

• Fecal calprotectin (to exclude colonic inflammation, especially in patients <40 years suspected of having IBS) 4, 5
• Fecal immunochemical test (FIT) for occult blood 4
• Giardia testing 4

Secondary Testing When Initial Workup is Normal

For suspected bile acid diarrhea (common in functional diarrhea/IBS-D):

• SeHCAT testing (first choice where available)
• Serum 7α-hydroxy-4-cholesten-3-one (bile acid precursor)
• Do NOT use empirical treatment trials instead of making a positive diagnosis 4, 5

For suspected microscopic colitis:

• Colonoscopy with biopsies from right and left colon (not rectum) 4, 5

For suspected malabsorption:

• Fecal elastase (for pancreatic insufficiency) - do NOT use PABA testing 4
• Comprehensive stool biochemical analysis: osmolality, pH, electrolytes (to differentiate osmotic from secretory diarrhea and identify laxative abuse) 2
• Hydrogen breath testing for lactose maldigestion (if available), or trial dietary lactose withdrawal 4

For structural abnormalities:

• MR enterography (preferred over CT or barium studies) 4
• Video capsule endoscopy 4

Special Populations

Immunocompromised patients require broader differential:

• Expanded bacterial, viral, and parasitic testing
• Consider opportunistic infections 1

Outbreak settings:

• Test broader panel of bacterial, viral, and parasitic agents regardless of fever or bloody stools
• Coordinate with public health authorities 1

Common Pitfalls to Avoid

• Do NOT perform exhaustive testing to exclude all organic pathology in suspected IBS - this is counterproductive and unnecessary 5
• Do NOT use small bowel barium studies - poor sensitivity and specificity 4
• Do NOT routinely perform hydrogen breath tests for small intestinal bacterial overgrowth - use empirical antibiotic trial instead 4, 5
• Do NOT test for C. difficile with single-step methods - requires two-step approach to avoid false positives from colonization 2
• Do NOT use antibiotics for acute watery diarrhea unless visible blood in stool (use ciprofloxacin as first-line) 6, 7

The strength of these recommendations comes primarily from the 2017 IDSA guidelines for infectious diarrhea 1 and the 2018 British Society of Gastroenterology guidelines for chronic diarrhea 4, both representing high-quality, society-endorsed guidance that should frame clinical decision-making.