What is the appropriate management for a patient with chronic infectious diarrhea lasting more than two weeks, including diagnostic workup, rehydration, dietary measures, and pathogen‑specific therapy?

Management of Chronic Infectious Diarrhea

Initial Rehydration (First Priority)

Rehydration is the most critical initial intervention and must be addressed immediately before any diagnostic workup or antimicrobial therapy. 1, 2

• For mild-to-moderate dehydration: Administer oral rehydration solution (ORS) at 50-100 mL/kg over 2-4 hours using WHO-recommended formulations containing sodium 90 mM, potassium 20 mM, chloride 80 mM, bicarbonate 30 mM, and glucose 111 mM 1, 2
• For severe dehydration: Initiate immediate intravenous rehydration with Ringer's lactate or normal saline until mental status and perfusion normalize 2
• Replace ongoing losses with approximately 10 mL/kg ORS for each watery stool and 2 mL/kg for each vomiting episode 2
• Continue appropriate fluid and electrolyte replacement throughout the entire treatment course 2

Diagnostic Workup

Standard Testing for Chronic Infectious Diarrhea (≥14 days)

All patients with diarrhea lasting 14 days or longer require comprehensive stool testing for both bacterial and parasitic pathogens. 1, 3

Bacterial pathogens to test:

• Salmonella, Shigella, Campylobacter, Yersinia via stool culture 3
• Clostridium difficile toxin testing, especially if antibiotic exposure within preceding 8-12 weeks 1, 3
• Shiga toxin-producing E. coli (STEC) with specific Shiga toxin testing 3

Parasitic evaluation:

• Stool examination for ova and parasites including Giardia lamblia, Cryptosporidium, Cyclospora, Cystoisospora, and Entamoeba histolytica 1, 3
• Giardia is the most common parasitic cause and should be specifically tested using antigen detection or multiplex PCR 4, 5

Baseline laboratory assessment:

• Complete blood count (CBC), C-reactive protein (CRP), and basic metabolic panel to assess inflammation, dehydration, and electrolyte abnormalities 3
• Fecal lactoferrin or calprotectin to detect inflammatory processes in bloody or inflammatory diarrhea 3

Immunocompromised Patients Require Expanded Testing

Immunocompromised patients must undergo additional testing beyond standard bacterial and parasitic workup. 1

• Test for Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus (CMV) 1
• Consider fungal pathogens including Candida albicans, particularly in patients on long-term antibiotics or antifungals 5

Important Diagnostic Considerations

Multiplex nucleic acid amplification tests (MP-NAAT) detect DNA, not viable organisms, requiring careful clinical interpretation. 1, 3

• Positive MP-NAAT results may represent non-viable organisms or colonization rather than active infection 1
• Specimens testing positive by culture-independent methods should be cultured when antimicrobial susceptibility testing would affect management or for public health reporting 1

Pathogen-Specific Antimicrobial Therapy

General Principles

Empiric antimicrobial therapy is NOT recommended for chronic watery diarrhea in immunocompetent patients without pathogen identification. 2

Antimicrobial therapy should be pathogen-directed based on stool testing results rather than empiric. 1, 2

Specific Pathogen Treatment

For Giardia lamblia (most common parasitic cause):

• Metronidazole is first-line therapy 6, 7
• Approximately 81% of pathogenic parasites identified in chronic diarrhea are likely metronidazole-sensitive 7

For bacterial pathogens:

• Treatment decisions should be guided by local antimicrobial resistance patterns and susceptibility testing 1
• Fluoroquinolones (e.g., ciprofloxacin) or azithromycin for susceptible bacterial pathogens in adults 2

For immunocompromised patients:

• Empiric treatment may be warranted while awaiting culture results given higher risk of severe illness 2, 5
• Consider both usual and unusual pathogens, including opportunistic organisms 5

Dietary Measures

Resume age-appropriate diet immediately after rehydration is achieved. 6

• Continue breastfeeding if applicable 6
• No specific dietary restrictions are required for most infectious diarrhea beyond lactose avoidance if lactose intolerance develops 1

When to Consider Non-Infectious Causes

If diarrhea persists beyond 14 days with negative infectious workup, non-infectious etiologies must be evaluated. 1

• Consider inflammatory bowel disease (IBD), microscopic colitis, post-infectious irritable bowel syndrome (IBS), and lactose intolerance 1
• Post-infectious enteropathy can cause prolonged symptoms mimicking ongoing infection 6, 4
• Infectious diarrhea can trigger IBD, IBS, or "Brainerd-type" diarrhea 4

Reassessment and Follow-Up

Patients not responding to initial therapy require clinical and laboratory reevaluation. 1

• Reassess fluid and electrolyte balance, nutritional status, and optimal antimicrobial dose/duration 1
• Consider endoscopic evaluation with colonoscopy for persistent symptoms with negative workup, especially in patients >45 years 3
• Duodenal aspirate may be useful for diagnosing Giardia and Strongyloides when stool evaluation is unrevealing 1

Follow-up stool testing is NOT routinely recommended after symptom resolution in most cases. 1

• Repeat cultures may be required by local health authorities for food handlers, childcare workers, or healthcare workers with Salmonella, STEC, or Shigella to enable return to work 1
• Use traditional culture methods for proof of cure, not culture-independent diagnostic tests 1

Common Pitfalls to Avoid

• Do not delay rehydration while awaiting diagnostic results—dehydration is the primary immediate risk 1, 2
• Avoid empiric antibiotics in immunocompetent patients with chronic watery diarrhea without pathogen identification 2
• Do not use loperamide in patients with bloody diarrhea, high fever, or suspected inflammatory/invasive diarrhea 2
• Remember to test for C. difficile even in outpatients if antibiotic exposure occurred within 8-12 weeks 1, 3
• Do not over-interpret positive MP-NAAT results without clinical correlation, as they detect DNA not viable organisms 1, 3