What is the workup and treatment for a patient with diarrhea lasting 2 weeks?

Workup for Diarrhea Lasting 2 Weeks

For diarrhea persisting 2 weeks, initiate empiric azithromycin 500 mg daily for 3 days combined with loperamide 4 mg initially then 2 mg after each loose stool (maximum 16 mg/day), while simultaneously obtaining stool studies for bacterial pathogens and C. difficile. 1, 2

Initial Clinical Assessment

Immediately evaluate for the following critical features that determine management pathway:

• Red flag symptoms requiring urgent evaluation: bloody stools, fever >38.5°C, severe abdominal pain, signs of dehydration (tachycardia, orthostatic hypotension, urine output <0.5 mL/kg/hr), weight loss, or immunosuppression 3, 4, 5
• Hydration status: Check for tachycardia, orthostatic vital signs, decreased urine output, and altered mental status 3
• Immunocompromised state: Active chemotherapy, neutropenia (ANC <500), chronic immunosuppressors, or HIV 6, 3

Diagnostic Workup

For Uncomplicated Watery Diarrhea (No Red Flags)

• Stool studies: Culture for Salmonella, E. coli, Campylobacter, Shigella, and C. difficile toxin 6, 3
• Laboratory tests: Complete blood count, electrolyte panel, renal function 6, 3
• Most patients with 2-week duration warrant testing given persistence beyond typical viral gastroenteritis 5

For Complicated Diarrhea (Any Red Flags Present)

• Immediate hospitalization if bloody diarrhea with fever, neutropenia, sepsis signs, or severe dehydration 6, 3
• Complete workup: CBC with differential, comprehensive metabolic panel, blood cultures if febrile, stool for blood, pathogens, and C. difficile 6, 3

Treatment Algorithm

Uncomplicated Cases (Watery, No Red Flags)

First-line therapy:

• Azithromycin 500 mg PO daily for 3 days (preferred over fluoroquinolones due to Campylobacter resistance) 1, 2
• Loperamide 4 mg initially, then 2 mg after each loose stool or every 4 hours, maximum 16 mg/day 6
• Oral rehydration solution targeting urine output >0.5 mL/kg/hr 1
• Dietary modifications: Eliminate lactose, avoid caffeine/alcohol/spices, bland diet (bananas, rice, applesauce, toast) 6

The combination of antibiotic plus loperamide is significantly more effective than antibiotic alone, with 63% of patients passing no further unformed stools after initial doses and 91% well within 24 hours 7.

Complicated Cases (Bloody Diarrhea, Fever, or Immunosuppression)

Immediate management:

• Hospital admission with IV fluid resuscitation: 20 mL/kg bolus if tachycardic or septic 3, 1
• Broad-spectrum IV antibiotics immediately (before culture results): Piperacillin-tazobactam OR imipenem-cilastatin monotherapy, OR cefepime/ceftazidime PLUS metronidazole 6, 3
• Avoid loperamide and opioids in bloody diarrhea, fever, or neutropenia as they may worsen ileus and mask invasive disease 6, 3, 5

If Diarrhea Persists Despite Initial Treatment (48-72 Hours)

Escalation therapy:

• Octreotide 100-150 mcg subcutaneous three times daily, escalating to 500 mcg three times daily if needed 6
• Consider IV octreotide 25-50 mcg/hr if severe dehydration present 6
• Reassess for alternative diagnoses: inflammatory bowel disease, malabsorption syndromes, parasitic infections 4

Special Considerations

Neutropenic Enterocolitis

If neutropenic (ANC <500) with bloody diarrhea:

• Absolutely avoid antimotility agents (loperamide, opioids, anticholinergics) as they aggravate ileus 6, 3
• Broad-spectrum antibiotics covering gram-negatives, gram-positives, and anaerobes 6, 3
• G-CSF administration 6, 3
• Surgical consultation for persistent GI bleeding after correcting coagulopathy, free perforation, abscess formation, or clinical deterioration 6, 3

When to Discontinue Loperamide

• Stop after 12-hour diarrhea-free interval in uncomplicated cases 6
• Discontinue immediately if fever develops, blood appears in stool, or severe abdominal pain occurs 1, 5

Common Pitfalls

• Do not delay antibiotics in persistent diarrhea beyond 5 days—azithromycin is safe and effective even without confirmed bacterial etiology 1, 2
• Do not use fluoroquinolones as first-line due to widespread Campylobacter resistance 1, 2
• Do not withhold loperamide in watery diarrhea due to unfounded fears—large trials show safety and efficacy when used appropriately 8, 7
• Do not use loperamide with any signs of invasive disease—this is the critical contraindication 1, 5