What labs should be drawn for a gastrointestinal (GI) infection workup?

Laboratory Workup for Gastrointestinal Infection

For acute GI infections, obtain a complete blood count, comprehensive metabolic panel, inflammatory markers (CRP), and stool testing that includes multiplex molecular diagnostics or culture for bacterial pathogens (Salmonella, Shigella, Campylobacter, E. coli O157:H7), plus separate C. difficile testing in patients with recent antibiotic exposure or healthcare-associated diarrhea. 1

Initial Blood Work

Complete Blood Count and Chemistry Panel:

• Full blood count including hemoglobin, white blood cell count with differential, and platelet count 1
• Comprehensive metabolic panel with electrolytes, renal function (BUN, creatinine), and liver enzymes 1
• C-reactive protein (CRP) is superior to erythrocyte sedimentation rate (ESR) for evaluating acute GI infections 1
• Serum albumin and pre-albumin to assess nutritional status and degree of inflammation 1
• Serum lactate if ischemic colitis or severe infection is suspected (levels ≥2.0 mmol/L indicate non-viable bowel) 2

Stool Testing Strategy

Specimen Collection:

• The optimal specimen is a diarrheal stool sample that takes the shape of the container 1
• If timely diarrheal stool cannot be collected, a rectal swab may be used for bacterial detection, though molecular techniques are less dependent on specimen quality 1
• A single diarrheal stool specimen is sufficient; multiple specimens do not increase yield 1

Primary Stool Tests:

Bacterial Pathogens:

• Routine stool culture or multiplex molecular diagnostics should detect four primary bacterial enteric pathogens: Salmonella, Shigella, Campylobacter, and E. coli O157:H7/Shiga toxin-producing E. coli 1, 3
• Multiplex antimicrobial testing is now preferred over traditional stool cultures and microscopic examinations 4
• Culture-independent diagnostic testing (gastrointestinal panels) detects DNA, not necessarily viable organisms, so clinical context is critical for interpretation 1
• Specimens testing positive by molecular assays should be cultured if isolate submission is required for public health reporting or antimicrobial susceptibility testing 1

Specialized Bacterial Testing (when indicated):

• Yersinia, Vibrio, and Plesiomonas require specialized culture or molecular assays beyond routine stool culture 3
• Clostridium perfringens requires specialized toxin detection 3

Clostridium difficile Testing

When to Test:

• Test patients >2 years of age with diarrhea following antimicrobial use 1
• Test patients with healthcare-associated diarrhea 1
• Consider testing in travelers treated with antimicrobials within the preceding 8-12 weeks 1
• May consider in patients with persistent diarrhea without etiology and without recognized risk factors 1

Testing Methodology:

• Use a two-step algorithm: first detect the organism with glutamate dehydrogenase (GDH) enzyme immunoassay or nucleic acid amplification testing (NAAT/PCR), then confirm toxin production with toxin EIA 1
• This combination provides high negative and positive predictive values when tests agree 1
• Do not use toxin EIA alone due to low sensitivity 1
• Do not rely on PCR alone without toxin confirmation, as this may detect asymptomatic colonization 1
• A single stool specimen is sufficient; repeat testing during the same diarrheal episode is not recommended unless high clinical suspicion persists 1

Parasitic Testing

When to Test:

• Travelers with diarrhea lasting ≥14 days should be evaluated for intestinal parasitic infections 1
• Consider in patients with exposure to endemic areas, untreated water, day-care settings, or men who have sex with men 1

Testing Methods:

• Examination of three fresh stools for ova, cysts, and parasites has 60-90% sensitivity for Giardia and Entamoeba 1
• Stool ELISA for Giardia antigen has 92% sensitivity and 98% specificity, largely replacing the need for intestinal biopsies 1
• Multiplex panel tests for parasites show 100% sensitivity for Cryptosporidium and Giardia with high specificity 1

Additional Inflammatory Markers

Fecal Calprotectin:

• Useful for differentiating inflammatory from non-inflammatory causes of diarrhea 1
• Levels >50 μg/g suggest inflammatory bowel disease is more likely than irritable bowel syndrome 1
• Helps guide need for further invasive testing 1

Special Circumstances

Enteric Fever or Bacteremia:

• Obtain blood cultures in addition to stool testing when enteric fever (typhoid) or bacteremia is suspected 1
• Bone marrow culture is particularly valuable if antimicrobials have been administered 1
• Do not use serologic tests to diagnose enteric fever 1

Immunocompromised Patients:

• HIV testing should be performed in immunocompromised patients with chronic diarrhea 1
• Consider testing for Cryptosporidium, Cytomegalovirus, and other opportunistic pathogens 1

Common Pitfalls to Avoid

• Do not order C. difficile testing on formed stools or asymptomatic patients 1
• Do not interpret positive C. difficile PCR without toxin confirmation as definitive infection, as this may represent colonization 1
• Do not repeat C. difficile testing after initial negative result during the same episode unless high clinical suspicion or outbreak situation 1
• Do not rely solely on clinical laboratories for outbreak detection; submit positive isolates to public health laboratories for epidemiologic typing 1, 3
• Do not order stool cultures for chronic diarrhea (>14 days) in immunocompetent patients without travel history, as bacterial causes are rare 1