Which diagnostic tests should be performed for a 60‑year‑old woman with several weeks of diarrhea that began after recent four‑week travel, one month of broad‑spectrum antibiotic use, a recent hospital admission, and family gatherings, given negative COVID‑19, streptococcal, and influenza tests?

Diagnostic Testing for Persistent Diarrhea with Multiple Risk Factors

This 60-year-old woman requires immediate Clostridioides difficile testing given her recent antibiotic use and hospital admission, along with comprehensive stool studies for bacterial pathogens and parasites given her 4-week travel history. 1

Immediate Priority Testing

C. difficile Testing (Highest Priority)

• Test for C. difficile toxin immediately given the combination of recent broad-spectrum antibiotic use (within 1 month) and recent hospitalization—both are the strongest risk factors for C. difficile-associated diarrhea 1
• C. difficile accounts for 10-20% of antibiotic-associated diarrhea cases and is the most common cause of nosocomial diarrhea 2, 3
• The recent hospital admission creates additional risk for healthcare-acquired C. difficile infection 1, 3

Comprehensive Stool Studies

Order the following fecal tests given diarrhea lasting >1 day with recent antibiotic use, hospitalization, and travel history: 1

• Bacterial stool culture for Salmonella, Shigella, Campylobacter, and Yersinia 1, 4
• Stool testing for Shiga toxin-producing E. coli (STEC) 1
• Ova and parasite examination with specific testing for:
  • Giardia antigen
  • Cryptosporidium antigen
  • Cyclospora (given travel history) 1, 4
  • Entamoeba histolytica antigen 1, 4

Fecal Inflammatory Markers

• Fecal lactoferrin or fecal leukocytes to assess for inflammatory diarrhea, which would suggest invasive bacterial pathogens or inflammatory bowel disease 1
• Fecal occult blood testing to identify bloody diarrhea that may not be grossly visible 1

Additional Laboratory Testing

Complete Blood Count with Differential

• Check for eosinophilia, which would suggest parasitic infection, particularly if she had freshwater exposure during travel 4
• Assess for leukocytosis, which may indicate bacterial infection or C. difficile colitis 1, 5

Basic Metabolic Panel

• Evaluate for dehydration and electrolyte abnormalities given 4 weeks of diarrhea 1
• Check for signs of volume depletion including elevated BUN/creatinine ratio 1

Travel-Specific Considerations

Protozoal Pathogens (Higher Yield in Persistent Diarrhea)

• Persistent diarrhea (>14 days) has higher frequency of protozoal pathogens including Cryptosporidium, Giardia, Cyclospora, and Entamoeba histolytica 1, 4
• Three daily stool samples increase diagnostic yield for parasites 4

Consider Empirical Treatment for Giardiasis

• If initial stool studies are negative and diarrhea persists >10-14 days with suggestive travel history, empirical treatment for giardiasis may be considered 1

COVID-19 Considerations (Already Tested Negative)

• While COVID-19 can present with diarrhea in 10-20% of cases and GI symptoms may precede respiratory symptoms, her negative COVID-19 test makes this unlikely 1, 6
• Do not perform stool testing for COVID-19 as there is inadequate evidence to support this for diagnosis or monitoring 1, 7

Critical Pitfalls to Avoid

Don't Overlook Antibiotic-Associated Causes

• Beyond C. difficile, consider other antibiotic-associated pathogens including Klebsiella pneumoniae, Candida species, and Staphylococcus aureus, which collectively may cause antibiotic-associated diarrhea 2
• Antibiotics cause direct toxic effects on intestinal function and alter normal flora 2, 8

Don't Assume Simple Travelers' Diarrhea

• Four weeks of diarrhea is NOT typical travelers' diarrhea, which usually resolves in 3-5 days without treatment 1, 4
• The persistence beyond 2 weeks mandates comprehensive microbiologic evaluation 1, 4

Don't Miss the Family Gathering Connection

• The family gathering represents potential foodborne outbreak exposure—ask specifically about other family members with similar symptoms 1
• If multiple family members are affected, this increases likelihood of common-source foodborne pathogen 1

Avoid Fluoroquinolones if Empirical Treatment Needed

• Do not use fluoroquinolones empirically given increasing resistance patterns, particularly from Caribbean/Asian travel destinations 4
• Azithromycin (1 gram single dose or 500 mg daily for 3 days) is preferred for severe diarrhea with systemic symptoms 4

When to Consider Additional Testing

If Initial Studies Are Negative

• Serum chemistry panel, abdominal imaging, or colonoscopy may be warranted if symptoms persist despite negative initial workup and optimized medical management 1
• Consider consultation with infectious disease or gastroenterology if diagnosis remains elusive 4