Can cefepime and vancomycin cause diarrhea in patients?

Can Cefepime and Vancomycin Cause Diarrhea?

Yes, both cefepime and vancomycin can cause diarrhea, but through different mechanisms: cefepime primarily causes antibiotic-associated diarrhea (AAD) including Clostridioides difficile infection (CDI), while vancomycin causes diarrhea only when given intravenously (oral vancomycin treats rather than causes diarrhea).

Cefepime and Diarrhea Risk

Mechanism of Diarrhea

• Cefepime, as a cephalosporin, is strongly associated with antibiotic-associated diarrhea and CDI 1.
• Cephalosporins are among the antibiotic classes most strongly linked to CDI, along with clindamycin, aminopenicillins, and fluoroquinolones 1.
• The incidence of AAD with antibiotics ranges from 5-25%, with CDI accounting for 10-20% of all AAD cases 2.

Clinical Context

• When cefepime is used in combination regimens for neutropenic enterocolitis (along with metronidazole), the broad-spectrum coverage disrupts normal intestinal flora, predisposing to CDI 1.
• Cefepime is recommended as part of empirical therapy for neutropenic enterocolitis specifically because it covers enteric pathogens, but this same broad coverage increases AAD risk 1, 3.

Vancomycin and Diarrhea: Route-Dependent Effects

Oral Vancomycin Does NOT Cause Diarrhea

• Oral vancomycin is the treatment for CDI-associated diarrhea, not a cause 1.
• Oral vancomycin achieves high fecal concentrations and eliminates C. difficile toxins, resolving diarrhea in 87% of patients within 48 hours 4.
• Vancomycin 125 mg four times daily orally for 10 days is first-line therapy for CDI 1.

Intravenous Vancomycin: Minimal Direct Diarrhea Risk

• Intravenous vancomycin has minimal systemic absorption into the gastrointestinal tract and does not directly cause diarrhea through intestinal mechanisms 1.
• However, like any systemic antibiotic, IV vancomycin can theoretically contribute to AAD by altering gut flora, though this is not a commonly reported adverse effect.
• The evidence focuses on IV vancomycin's role in treating systemic infections, not causing gastrointestinal complications 5.

Critical Clinical Pitfalls

When Diarrhea Develops on These Antibiotics

• If diarrhea develops in a patient receiving cefepime (with or without vancomycin), immediately test for C. difficile toxin 1, 6.
• Do not use antiperistaltic agents (loperamide, opiates) as they may precipitate toxic megacolon 1, 6.
• Discontinue the causative antibiotic (cefepime) if clinically feasible 1, 6.

Testing and Diagnosis

• Test only symptomatic patients with ≥3 unformed stools in 24 hours who have antibiotic exposure, healthcare exposure, or immunosuppression 6.
• Use multistep algorithms combining PCR for toxin genes with toxin enzyme immunoassay for optimal diagnostic performance 6.
• Never test asymptomatic patients or perform "test of cure" after treatment 6, 7.

Empirical Treatment Considerations

• If severe disease is suspected (leukocytosis ≥15 × 10⁹ cells/L, fever, abdominal pain), start empirical oral vancomycin 125 mg four times daily immediately without waiting for test results 6.
• For neutropenic patients with diarrhea on cefepime-based regimens, empirical metronidazole may be considered in severe cases while awaiting CDI testing 1.

Management Algorithm

Step 1: Assess Severity

• Mild diarrhea (grade 1-2): Conservative management with oral hydration and loperamide 1.
• Severe diarrhea or complications (fever, neutropenia, bleeding, dehydration): Hospitalize and evaluate for CDI 1.

Step 2: Test for CDI

• Obtain stool for C. difficile testing in all patients with ≥3 unformed stools in 24 hours on cefepime 6.
• If severe disease indicators present, start empirical vancomycin while awaiting results 6.

Step 3: Modify Antibiotic Regimen

• Discontinue cefepime if clinically feasible 1, 6.
• If continued broad-spectrum coverage needed, consider switching to agents with lower CDI risk 1.
• Continue IV vancomycin if needed for systemic infection (it does not contribute to diarrhea) 5.

Step 4: Treat CDI if Confirmed

• Non-severe CDI: Oral vancomycin 125 mg four times daily or metronidazole 500 mg three times daily for 10 days 1.
• Severe CDI: Oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days 1.

Recurrence Risk

• Symptomatic relapse occurs in approximately 14% of patients after vancomycin therapy for CDI 8.
• Recurrence rates are 7-20% and result from both relapse and reinfection 7.
• First recurrences respond to retreatment with the same regimen in over 90% of cases 7.