What should be done if a patient develops diarrhea while taking Augmentin (amoxicillin‑clavulanate)?

Management of Augmentin-Induced Diarrhea

Diarrhea from Augmentin is common and usually self-limited, but requires a stepwise approach based on severity—mild cases respond to dietary modifications and loperamide, while severe or persistent cases warrant discontinuation and evaluation for C. difficile infection.

Understanding the Problem

Diarrhea is one of the most common adverse effects of amoxicillin-clavulanate (Augmentin), occurring in approximately 23% of patients, particularly in children under 2 years of age 1. The FDA label explicitly states that diarrhea is a common problem caused by antibacterials and usually ends when the drug is discontinued 2. The clavulanate component is the primary culprit—when doses exceed approximately 10 mg/kg per day, diarrhea becomes particularly problematic 3.

Initial Assessment and Red Flags

First, determine if this is uncomplicated antibiotic-associated diarrhea or something more serious:

• Uncomplicated diarrhea: Loose stools without blood, no fever, no severe abdominal cramping, no signs of dehydration 3
• Complicated diarrhea requiring immediate attention: Watery and bloody stools, fever with diarrhea, severe abdominal cramping, signs of dehydration, or diarrhea persisting beyond 48-72 hours 2, 3

The FDA specifically warns that patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after the last dose, suggesting possible C. difficile infection 2.

Management Algorithm

For Uncomplicated Diarrhea (Mild, No Warning Signs)

Continue Augmentin if clinically necessary and implement supportive measures:

• Take each dose with food: The FDA label recommends taking each dose with a meal or snack to reduce gastrointestinal upset 2
• Dietary modifications: Eliminate lactose-containing products, avoid high-fat foods and high-osmolar supplements 3, 4
• Increase fluid intake: Drink 8-10 large glasses of clear liquids daily to prevent dehydration 4
• Start loperamide: Initial dose of 4 mg, then 2 mg every 4 hours or after every unformed stool (maximum 16 mg/day) 3, 4
• Monitor closely: Record number of stools daily and watch for warning signs 4

For Persistent Diarrhea (24-48 Hours Despite Loperamide)

Consider C. difficile infection and escalate management:

• Discontinue Augmentin if the infection being treated allows for it 2
• Obtain stool studies: Test for C. difficile toxins, as toxigenic C. difficile was found in 27% of children with diarrhea after amoxicillin-clavulanate therapy 5
• Consider empiric fluoroquinolone: If diarrhea persists beyond 24 hours on loperamide, some guidelines recommend adding oral fluoroquinolone for 7 days, particularly if fever is present 3

For Severe or Complicated Diarrhea

Stop Augmentin immediately and hospitalize:

• Discontinue loperamide and stop Augmentin 3, 2
• Hospitalize for IV fluids: Administer intravenous isotonic fluids for rehydration 3
• Obtain complete workup: CBC, comprehensive metabolic panel, stool studies for C. difficile, blood cultures if febrile 3
• Consider octreotide: For refractory cases, start subcutaneously at 100-150 μg three times daily, with escalation up to 500 μg three times daily if needed 3, 4
• Broad-spectrum antibiotics: If neutropenic or septic, initiate coverage for gram-negative, gram-positive, and anaerobic organisms 3

Special Considerations

Switching Formulations

Recent evidence suggests that lower clavulanate concentrations may reduce diarrhea while maintaining efficacy. A formulation providing 80 mg amoxicillin/2.85 mg clavulanate/kg/day resulted in significantly less diaper dermatitis (21% vs 33%, P=0.04) compared to standard dosing, with no significant difference in treatment failure rates 6. Consider discussing with the prescriber whether a twice-daily formulation (which contains less total daily clavulanate) might be appropriate 3.

Pediatric Patients

Children under 2 years have an 18% incidence of antibiotic-associated diarrhea compared to only 3% in older children 1. These younger patients require more vigilant monitoring for dehydration and may benefit from lower clavulanate formulations 6.

Critical Pitfalls to Avoid

• Never use loperamide if bloody diarrhea, fever, or severe abdominal pain is present, as this may mask serious complications like C. difficile colitis or hemorrhagic colitis from cytotoxin-producing Klebsiella oxytoca 7, 8
• Do not assume all diarrhea is benign: Antibiotic-associated hemorrhagic colitis from K. oxytoca can present with right-sided colitis and bloody diarrhea, requiring cessation of the antibiotic 7
• Contact physician if diarrhea is severe or lasts more than 2-3 days, as the FDA label explicitly recommends 2

When Augmentin Must Be Continued

If the infection being treated is serious and Augmentin cannot be discontinued, maximize supportive care with aggressive hydration, dietary modifications, and judicious use of loperamide while monitoring closely for complications 2. However, clinical judgment should favor stopping the antibiotic if diarrhea becomes severe, as the FDA label notes that diarrhea usually ends when the antibacterial is discontinued 2.