Antibiotic-Associated Diarrhea After Amoxicillin: Immediate Management
Stop the amoxicillin immediately and test for Clostridioides difficile infection, as this is the most critical step to prevent progression to severe colitis. 1
Immediate Actions Required
Discontinue amoxicillin now – The FDA label explicitly warns that amoxicillin causes Clostridioides difficile-associated diarrhea (CDAD), and continuing the antibiotic significantly worsens outcomes and increases recurrence risk. 1, 2
Test for C. difficile toxin – After 10 days of amoxicillin with 4 days of diarrhea, C. difficile infection must be ruled out, as amoxicillin is one of the antibiotics most commonly implicated in antibiotic-associated diarrhea. 3 The enzyme immunoassay for C. difficile toxin is a practical and reasonably accurate test. 3
Clinical Assessment to Guide Next Steps
Evaluate for severe disease indicators:
- Fever, severe abdominal cramps, or blood in stool – These suggest colitis rather than simple antibiotic-associated diarrhea and warrant urgent evaluation. 3
- Frequency and volume – More than 3-4 watery stools daily with systemic symptoms increases concern for C. difficile infection. 4
- White blood cell count >15,000 cells/μL or creatinine >1.5 mg/dL – These define severe C. difficile infection requiring immediate treatment. 2, 4
If C. difficile testing is positive:
Start vancomycin 125 mg orally four times daily for 10 days immediately – This is the IDSA/SHEA strongly recommended first-line treatment for initial C. difficile infection, superior to metronidazole. 2
Never use IV vancomycin – Parenteral vancomycin is completely ineffective for C. difficile infection as it does not reach the colon. 2
Avoid antidiarrheal medications completely – Loperamide and opiates worsen outcomes by promoting toxin retention and increasing risk of toxic megacolon. 2, 4
If C. difficile testing is negative:
Simple antibiotic-associated diarrhea typically resolves within 2-6 days after stopping the antibiotic. 5 However, amoxicillin can also cause hemorrhagic colitis, a distinct entity from C. difficile infection. 6, 5
Consider hemorrhagic colitis if bloody diarrhea is present – This typically occurs 4-6 days after starting amoxicillin and involves the right colon or descending/sigmoid colon, with negative C. difficile testing. 5 Management includes:
- Stopping the antibiotic (already done)
- Supportive care with probiotics (Bifidobacterium or Saccharomyces boulardii) 6
- Symptoms resolve rapidly within 2-6 days 5
Supportive Management
Hydration is essential – Maintain adequate fluid intake to prevent dehydration from ongoing diarrhea. 7
Probiotics may provide symptomatic benefit – While Saccharomyces boulardii did not prevent amoxicillin-associated diarrhea in one trial 8, case reports suggest benefit for hemorrhagic colitis recovery. 6
Red Flags Requiring Emergency Evaluation
- Severe abdominal pain with distension – May indicate toxic megacolon or fulminant colitis 4
- Hypotension or signs of shock – Defines fulminant C. difficile infection requiring high-dose vancomycin 500 mg four times daily plus IV metronidazole 2, 4
- Worsening symptoms after stopping amoxicillin – Suggests established C. difficile infection requiring treatment 2
Common Pitfalls to Avoid
Do not restart amoxicillin or any other antibiotic without treating confirmed C. difficile infection first, as this dramatically increases recurrence rates. 2
Do not wait for test results if severely ill – If you have fever >38.3°C, severe abdominal pain, or bloody diarrhea with leukocytosis, empiric vancomycin treatment should begin immediately while awaiting C. difficile testing. 9, 2
Do not assume it will resolve on its own – While simple antibiotic-associated diarrhea may self-resolve, C. difficile infection requires specific treatment and can progress to life-threatening colitis. 4, 1