What is the recommended treatment for an adult with mild-to-moderate, non-bloody, non-febrile acute diarrhea, including oral rehydration solution, antidiarrheal therapy, and indications for antibiotics or treatment of suspected Clostridioides difficile infection?

Treatment of Acute Diarrhea in Adults

Immediate Rehydration is the Priority

Begin reduced-osmolarity oral rehydration solution (65–70 mEq/L sodium, 75–90 mmol/L glucose) immediately for all adults with mild-to-moderate acute diarrhea; this is the single most important intervention to prevent morbidity and mortality. 1, 2

Oral Rehydration Protocol

• Prescribe 2,200–4,000 mL total fluid intake per day, calculated to exceed ongoing losses (urine output + 30–50 mL/hour insensible losses + stool volume). 2
• For mild dehydration (3–5% fluid deficit): Administer 50 mL/kg ORS over 2–4 hours. 2
• For moderate dehydration (6–9% fluid deficit): Administer 100 mL/kg ORS over 2–4 hours. 1, 2
• Continue ORS until clinical dehydration resolves and diarrhea stops—do not discontinue prematurely. 1, 2
• Commercial ORS products (Pedialyte, CeraLyte, Enfalac Lytren) are appropriate; avoid apple juice, Gatorade, and soft drinks due to inappropriate osmolarity. 1, 3

When to Switch to Intravenous Fluids

Administer isotonic IV fluids (lactated Ringer's or normal saline) immediately if any of the following are present: 1, 2

• Severe dehydration (≥10% fluid deficit) with altered mental status, prolonged skin tenting >2 seconds, cool extremities, or decreased capillary refill
• Shock or hypotension
• Inability to tolerate oral intake despite attempts
• Intestinal ileus
• Failure of oral rehydration after adequate trial

Continue IV fluids until pulse, perfusion, and mental status normalize, then transition to ORS to replace remaining deficit. 1, 4

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Dietary Management

Resume a normal, age-appropriate diet immediately after rehydration is achieved—early feeding prevents malnutrition and may reduce stool output. 1, 4

• Start with small, light meals and avoid fatty, heavy, spicy foods and caffeine during the acute phase. 2
• Avoid lactose-containing products, alcohol, and high-osmolarity supplements temporarily. 2
• Do not withhold food—this provides no benefit and worsens outcomes. 4

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Antidiarrheal Therapy (Loperamide)

Loperamide may be used in immunocompetent adults with watery diarrhea ONLY after adequate rehydration has been achieved. 1, 2

Dosing

• Initial dose: 4 mg, then 2 mg after each loose stool or every 2–4 hours, maximum 16 mg per day. 2, 3

Absolute Contraindications

Never use loperamide if any of the following are present: 1, 2, 4

• Fever ≥38.5°C
• Bloody or mucoid stools
• Suspected inflammatory diarrhea (risk of toxic megacolon)
• Age <18 years
• Suspected Shiga-toxin-producing E. coli (STEC) infection

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Antibiotic Therapy: When NOT to Prescribe

Do not prescribe empiric antibiotics for uncomplicated acute watery diarrhea in otherwise healthy adults without recent international travel—this is a strong recommendation to prevent antimicrobial resistance. 1, 2

Situations Where Antibiotics Are Indicated

Prescribe empiric antibiotics ONLY when any of the following are present: 1, 2

• Fever ≥38.5°C with bloody or mucoid stools (suggests invasive bacterial pathogens: Shigella, Campylobacter, invasive E. coli)
• Recent international travel with severe, incapacitating symptoms (travelers' diarrhea)
• Immunocompromised status with severe illness
• Clinical sepsis features (altered mental status, hypotension, tachycardia) with suspected enteric fever
• Ill-appearing infants <3 months when bacterial infection is suspected

Preferred Antibiotic Regimen

• Azithromycin is first-line: 500 mg single dose for watery diarrhea; 1,000 mg single dose for febrile dysentery. 2
• Fluoroquinolones are second-line (ciprofloxacin 750 mg single dose or levofloxacin 500 mg single dose) if azithromycin is unavailable or local susceptibility favors their use. 2

Critical Exception: Shiga-Toxin-Producing E. coli

Never prescribe antibiotics for suspected or confirmed STEC O157:H7 or Shiga-toxin-2-producing E. coli—antibiotics markedly increase the risk of hemolytic-uremic syndrome. 2, 4

• Obtain Shiga-toxin testing before starting antibiotics in any patient with bloody diarrhea. 2

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Suspected Clostridioides difficile Infection

When to Suspect CDI

Consider C. difficile infection in patients with: 5, 6, 7, 8

• Three or more episodes of unexplained, unformed stools in 24 hours
• Recent antibiotic exposure (especially clindamycin, ampicillin, amoxicillin, cephalosporins)
• Recent healthcare facility exposure or hospitalization
• Severe abdominal pain, fever, or leukocytosis

Diagnostic Testing

Test stool for C. difficile toxins using enzyme immunoassay for glutamate dehydrogenase and toxins A and B, or nucleic acid amplification testing. 8

• Do not test patients taking laxatives or those without risk factors. 8

Treatment of CDI

For initial episode of nonsevere CDI: 8

• Oral vancomycin (125 mg four times daily for 10 days) or oral fidaxomicin (200 mg twice daily for 10 days) is recommended. 8
• Metronidazole is no longer recommended as first-line therapy for adults. 8

For severe CDI (white blood cell count >15,000/μL or serum creatinine >1.5 mg/dL): 8

• Oral vancomycin 125 mg four times daily for 10 days is preferred. 8

For recurrent CDI (≥2 episodes): 6, 8

• Fecal microbiota transplantation is a reasonable option with high cure rates after appropriate antibiotic therapy for at least three episodes. 8

First step in management: 5, 7

• Discontinue the antibiotic that caused diarrhea if clinically feasible. 5

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Adjunctive Therapies

• Ondansetron may be used to control vomiting and improve tolerance of oral rehydration in adults with significant nausea. 4, 3
• Probiotics may be offered to reduce symptom severity and duration, though evidence is moderate and the Infectious Diseases Society of America does not recommend probiotics specifically for prevention of C. difficile infection. 2, 4, 8

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Critical Pitfalls to Avoid

• Never prioritize antimotility agents or antibiotics over rehydration—dehydration, not diarrhea, drives morbidity and mortality. 2, 3
• Never use loperamide when fever or bloody stools are present—risk of toxic megacolon. 1, 2, 4
• Never start antibiotics for bloody diarrhea before ruling out STEC with Shiga-toxin testing. 2
• Never prescribe empiric antibiotics for uncomplicated watery diarrhea—this promotes antimicrobial resistance without clinical benefit. 1, 2
• Never delay IV rehydration in severe dehydration while attempting oral rehydration. 1, 2
• Never use sports drinks, juice, or soft drinks for rehydration—incorrect osmolarity worsens electrolyte imbalances. 1, 3

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Reassessment and Follow-Up

• Reassess hydration status 2–4 hours after initiating rehydration therapy. 4
• If no clinical improvement within 48–72 hours, consider antimicrobial resistance, non-infectious etiologies, or need for hospitalization. 2
• Obtain stool cultures or microbiologic studies only if: symptoms persist >14 days, fever develops, bloody stools appear, or empiric therapy fails. 2