How should persistent diarrhea lasting more than two weeks be evaluated and managed?

Evaluation and Management of Persistent Diarrhea (≥2 Weeks)

For persistent diarrhea lasting 14 days or more, empiric antimicrobial therapy should be avoided, and evaluation should focus on parasitic infections rather than bacterial pathogens, with stool testing for Cryptosporidium, Giardia, Cyclospora, Cystoisospora, and Entamoeba histolytica. 1, 2, 3

Initial Clinical Assessment

Perform a targeted evaluation focusing on:

• Stool characteristics: Determine if watery versus bloody, frequency, volume, and presence of mucus 1
• Hydration status: Assess skin turgor, mucous membrane moisture, mental status, and capillary refill 4
• Travel history: Recent international travel suggests parasitic causes 1
• Immunocompromised status: HIV, transplant recipients, or immunosuppressive medications require broader testing 2
• Medication history: Recent antibiotic use (consider C. difficile), laxatives, or other medications 1
• Dietary exposures: Raw/undercooked meat, seafood, unpasteurized milk 1
• Red flag symptoms: Blood in stool, unintentional weight loss, fever, nocturnal diarrhea, palpable abdominal mass 3, 5

Rehydration (First Priority)

Oral rehydration solution (ORS) remains first-line therapy for mild to moderate dehydration regardless of diarrhea duration. 1, 3

• Administer reduced osmolarity ORS at 50-100 mL/kg over 2-4 hours for mild-moderate dehydration 1, 4
• Use intravenous lactated Ringer's or normal saline for severe dehydration, shock, altered mental status, or ileus 1
• Replace ongoing losses: approximately 10 mL/kg for each watery stool 4

Diagnostic Testing

Stool testing is mandatory for persistent diarrhea and should target parasitic pathogens specifically. 1, 2

Standard Testing Panel:

• Parasitic studies: Cryptosporidium, Giardia, Cyclospora, Cystoisospora, Entamoeba histolytica 1, 2
• Consider C. difficile testing if recent antibiotic exposure 4

Expanded Testing for Immunocompromised Patients:

• Add microsporidia, MAC (Mycobacterium avium complex), and CMV (cytomegalovirus) to the parasitic panel 2

When to Obtain Additional Studies:

• If diarrhea persists beyond 30 days (chronic diarrhea threshold), shift focus to non-infectious causes 2, 3
• Order complete blood count, inflammatory markers (CRP/ESR), celiac serology, thyroid function tests, and fecal calprotectin 3

Antimicrobial Therapy

Empiric antibiotics should be avoided in persistent watery diarrhea lasting ≥14 days. 1, 3, 4

This represents a critical distinction from acute diarrhea management:

• Empiric treatment provides no benefit and exposes patients to unnecessary harm 1
• Antibiotics are indicated only when a specific pathogen is identified on stool testing 1
• Asymptomatic contacts should not receive empiric or preventive therapy 1

Exceptions (Treat Empirically Only If):

• Immunocompromised patients with severe illness 1
• Young infants (<3 months) who are ill-appearing 1, 4
• Bloody diarrhea with fever suggesting invasive bacterial infection 1

Symptomatic Management

Loperamide may be used cautiously while awaiting test results, but must be avoided if bloody diarrhea develops. 3

• Loperamide is FDA-approved for acute nonspecific diarrhea in patients ≥2 years 2
• Antimotility agents are contraindicated with bloody diarrhea or proven STEC infection 1

Nutritional Management

• Continue human milk feeding in infants throughout the illness 1
• Resume age-appropriate usual diet immediately after rehydration 1
• Maintain adequate dietary intake during the maintenance phase 1

Transition to Chronic Diarrhea Evaluation

If diarrhea persists beyond 30 days, the etiology shifts predominantly to non-infectious causes requiring gastroenterological workup. 2, 3

Non-infectious causes to consider at the 30-day threshold:

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 3, 4
• Microscopic colitis 3
• Celiac disease 3
• Bile acid diarrhea 3
• Irritable bowel syndrome (affects 9-12% of population) 3
• Malabsorption syndromes 3
• Colorectal neoplasia 3

Red Flags Requiring Urgent Gastroenterology Referral

Alarm features mandate urgent colonoscopy with biopsies regardless of diarrhea duration. 3, 5

• Blood in stool 3, 5
• Unintentional weight loss 3, 5
• Clinical and laboratory signs of anemia 3, 5
• Palpable abdominal mass 3, 5
• Nocturnal diarrhea (suggests organic rather than functional etiology) 3

Common Pitfalls to Avoid

• Do not prescribe empiric antibiotics for persistent watery diarrhea – this differs fundamentally from acute diarrhea management and provides no benefit 1, 3
• Do not use antimotility agents with bloody diarrhea – particularly dangerous with STEC infections 1
• Do not delay parasitic testing – bacterial pathogens are unlikely after 14 days, but parasites remain common 1, 2
• Do not miss the 30-day threshold – this signals the need to shift from infectious to non-infectious diagnostic workup 2, 3