Is a mix of constipation and diarrhea more common with antibiotic-associated diarrhea (AAD) or Clostridioides difficile (C. diff) infection in a patient taking Augmentin (amoxicillin/clavulanate) 875?

Mixed Constipation and Diarrhea in Antibiotic-Associated Diarrhea vs. C. difficile Infection

A mixed pattern of constipation and diarrhea is more characteristic of antibiotic-associated diarrhea (AAD) rather than Clostridioides difficile infection (CDI), which typically presents with persistent watery diarrhea.

Clinical Differentiation Between AAD and CDI

Antibiotic-Associated Diarrhea (AAD)

• Occurs in 5-25% of patients taking antibiotics 1
• Can present with variable stool patterns including alternating constipation and diarrhea
• Often presents as mild, self-limiting watery diarrhea without systemic symptoms
• Typically develops through:
  • Loss of normal intestinal flora
  • Reduced colonic bacterial carbohydrate metabolism
  • Altered gut motility

C. difficile Infection (CDI)

• Presents with more consistent watery diarrhea (≥3 loose or watery stools in 24 hours) 2
• Often accompanied by:
  • Fever
  • Abdominal pain/cramping
  • Leukocytosis
  • Presence of fecal leukocytes 3
  • In severe cases, pseudomembranes visible on endoscopy 4

Risk Factors Related to Augmentin 875

Amoxicillin/clavulanate (Augmentin) is strongly associated with both AAD and CDI:

• Penicillins including amoxicillin/clavulanate are among the antibiotics most frequently implicated in both AAD and CDI 2, 5
• According to the FDA label for amoxicillin/clavulanate, diarrhea is reported in 14-15% of patients 5
• The FDA label specifically warns about the risk of C. difficile-associated diarrhea (CDAD) with amoxicillin/clavulanate use 5

Diagnostic Approach

For a patient on Augmentin 875 with mixed constipation and diarrhea:

1. Consider AAD first if:

   • Symptoms are mild to moderate
   • No systemic symptoms (fever, severe abdominal pain)
   • Mixed pattern of constipation and diarrhea

2. Test for C. difficile if:

   • Diarrhea is predominant (≥3 loose stools in 24 hours)
   • Presence of systemic symptoms
   • Symptoms persist or worsen
   • Patient has other risk factors for CDI

Testing Recommendations

• For suspected CDI: Test a single diarrheal stool specimen for C. difficile toxin or toxigenic strain 4
• Multiple specimens do not increase diagnostic yield 4

Management Approach

For Suspected AAD:

1. Consider discontinuing Augmentin if clinically appropriate
2. Increase fluid intake
3. Dietary modifications:
   • Reduce lactose intake
   • Temporarily reduce fiber intake during diarrheal episodes
   • Avoid gas-producing foods 4

For Suspected CDI:

1. Discontinue the causative antibiotic (Augmentin) when possible 4, 2
2. Initiate specific treatment:
   • For non-severe cases: Oral vancomycin (125 mg four times daily for 10 days) as first-line treatment 2
   • Alternative for non-severe cases: Oral metronidazole (500 mg three times daily for 10 days) 2

Important Caveats

• The mixed pattern of constipation and diarrhea more commonly suggests AAD, but does not rule out CDI
• CDI must be considered in all patients who present with diarrhea following antibiotic use, as stated in the FDA label for amoxicillin/clavulanate 5
• CDI can occur up to 2 months after antibiotic administration 5
• Patients with inflammatory bowel disease may have atypical presentations of CDI that can be confused with disease flares 4

Remember that while a mixed pattern of constipation and diarrhea is more suggestive of AAD, clinical vigilance for CDI is essential in any patient experiencing diarrhea while on antibiotics, particularly high-risk agents like amoxicillin/clavulanate.