What is the next step for a patient with diarrhea persisting more than 3 days?

Management of Diarrhea Persisting Beyond 3 Days

For diarrhea persisting more than 3 days, obtain a detailed clinical and exposure history, evaluate for dehydration, and initiate stool testing for bacterial, viral, and parasitic pathogens while starting aggressive oral rehydration therapy with reduced osmolarity ORS. 1, 2

Immediate Clinical Assessment

Evaluate for high-risk features that determine urgency and diagnostic approach:

• Assess hydration status by checking for dry mucous membranes, decreased skin turgor, tachycardia, orthostatic vital signs, decreased urination, or altered mental status 1
• Document fever (temperature ≥38.5°C suggests bacterial etiology), presence of blood or mucus in stool, and severity of abdominal pain 1
• Obtain exposure history including recent antibiotic use (within 8-12 weeks), international travel, daycare/healthcare/food service work, consumption of raw/undercooked foods, and contact with others who are ill 1
• Identify immunocompromised status including HIV/AIDS, immunosuppressive therapy, or chronic illness requiring urgent broader workup 1

Diagnostic Testing Strategy

Order stool studies based on clinical presentation:

• Stool culture and multiplex PCR panel for Salmonella, Shigella, Campylobacter, Yersinia, STEC (including Shiga toxin detection), and C. difficile in patients with fever, bloody stools, severe abdominal pain, signs of sepsis, recent antibiotics, or immunocompromise 1, 2
• Parasitic testing (including Giardia, Cryptosporidium, Cyclospora, Entamoeba histolytica) for persistent watery diarrhea, especially with travel history or water exposure 1, 3
• Blood cultures if fever with signs of sepsis, age <3 months, or suspected enteric fever 1
• Fecal lactoferrin or leukocytes can help identify inflammatory diarrhea but are not required if multiplex testing available 1

Rehydration Protocol (First Priority)

Oral rehydration is the cornerstone of treatment regardless of etiology:

• Administer reduced osmolarity ORS (50-90 mEq/L sodium) as first-line therapy for mild to moderate dehydration 1, 2
• Replace ongoing losses with 10 mL/kg ORS for each watery stool 2
• Continue ORS until clinical dehydration corrects and diarrhea resolves 1, 2
• Use intravenous fluids (lactated Ringer's or normal saline) only for severe dehydration, shock, altered mental status, or ORS failure 1

Antimicrobial Therapy Decision Algorithm

Do NOT start empiric antibiotics for watery diarrhea without fever, blood, or travel history 1, 2

Consider empiric antibiotics ONLY in these specific scenarios:

• Bloody diarrhea with fever (≥38.5°C documented in medical setting) plus severe abdominal pain suggesting bacillary dysentery: start ciprofloxacin 500-750 mg single dose or azithromycin 1000 mg single dose based on local resistance patterns 1, 4
• Recent international travel with fever ≥38.5°C or signs of sepsis: azithromycin preferred (500 mg daily for 3 days or 1000 mg single dose) 1, 4
• Infants <3 months with suspected bacterial etiology: third-generation cephalosporin 1
• Immunocompromised patients with severe illness and bloody diarrhea 1

Avoid antibiotics entirely if STEC suspected (bloody diarrhea without fever, especially in children) as they increase HUS risk 1

Symptomatic Management

Loperamide can be used cautiously once adequate hydration achieved:

• Initial dose 4 mg followed by 2 mg after each unformed stool, maximum 16 mg daily 1, 2, 5
• Do NOT use if bloody diarrhea, high fever, suspected STEC, or C. difficile infection 1, 5
• Avoid in children under 2 years (contraindicated due to respiratory depression risk) 5

Dietary Recommendations

• Resume age-appropriate diet immediately after rehydration; do NOT restrict food 1
• Avoid fatty foods, heavy meals, spices, caffeine, and alcohol during acute phase 1, 2
• Consider lactose avoidance temporarily as secondary lactase deficiency common 1, 2

When to Reassess or Refer

Reevaluate if no improvement within 48 hours of appropriate therapy:

• Consider non-infectious causes including inflammatory bowel disease, irritable bowel syndrome, bile acid malabsorption, or medication side effects if symptoms persist ≥14 days 1
• Refer to gastroenterology for red flag symptoms: significant weight loss, severe abdominal pain mimicking appendicitis, palpable abdominal mass, or persistent symptoms despite treatment 6
• Monitor for HUS in confirmed STEC cases with frequent hemoglobin, platelet, electrolyte, and renal function checks 1

Critical Pitfalls to Avoid

• Never use empiric antibiotics for simple watery diarrhea as this promotes resistance, provides no benefit, and may worsen STEC outcomes 1, 2
• Never neglect rehydration while focusing on antimotility agents—dehydration causes the morbidity and mortality, not the diarrhea itself 1, 2
• Never give loperamide with bloody diarrhea or high fever as this can worsen invasive bacterial infections and increase toxic megacolon risk 1, 5
• Never assume viral etiology in immunocompromised patients—they require comprehensive bacterial, viral, and parasitic workup 1