What is the recommended management for patients at risk of Clostridioides difficile (C. diff) infection who are taking Proton Pump Inhibitors (PPIs)?

Management of Patients at Risk of C. difficile Infection Taking PPIs

Unnecessary PPIs should be discontinued in patients at risk for or with active C. difficile infection as part of good antimicrobial stewardship practice. 1, 2

Risk Association Between PPIs and C. difficile

• Multiple meta-analyses have demonstrated a significant association between PPI use and increased risk of C. difficile infection (CDI), with odds ratios ranging from 1.69 to 2.34 1, 3
• The combined effect of recent PPI and antibiotic use significantly increases CDI risk (OR=17.51) compared to either antibiotics alone (OR=15.37) or PPIs alone (OR=2.65) 4
• PPI use is also associated with a 42% increased risk of recurrent CDI (HR=1.42) 5
• The risk is highest in patients older than 80 years (HR=1.86) and those receiving antibiotics not targeted to C. difficile during follow-up (HR=1.71) 5

Decision-Making Algorithm for PPI Management

1. Evaluate PPI necessity:

   • Discontinue PPIs if no clear indication exists 2
   • Common inappropriate indications include stress ulcer prophylaxis in non-ICU patients, uncomplicated GERD after symptom resolution, or prophylaxis in low-risk patients on anticoagulants 2

2. For patients with legitimate PPI indications:

   • Consider the risk-benefit ratio carefully 2
   • Use the minimum effective dose required to treat symptoms 2
   • Consider temporary discontinuation during acute CDI treatment if clinically feasible 2

3. For patients on both antibiotics and PPIs:

   • Discontinue the inciting antibiotic agent(s) as soon as possible when treating CDI 2, 6
   • If continued antibiotic therapy is required, consider using antimicrobials less frequently implicated with CDI 6
   • Avoid high-risk antibiotics when possible (clindamycin, third-generation cephalosporins, penicillins, and fluoroquinolones) 6
   • Consider lower-risk antibiotics if clinically appropriate (aminoglycosides, sulfonamides, macrolides, tetracyclines) 6

Additional Risk Mitigation Strategies

• Minimize the duration of antibiotic therapy to reduce CDI risk 1
• The risk of CDI increases with the number of antibiotics prescribed - compared to patients receiving only 1 antibiotic, the adjusted hazard ratios for those receiving 2,3-4, or ≥5 antibiotics were 2.5,3.3, and 9.6, respectively 1
• For patients with CDI, avoid antimotility agents that can mask symptoms and potentially worsen outcomes 7
• Provide appropriate CDI treatment based on severity: oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days 7

Important Clinical Considerations

• While the association between PPI use and CDI is epidemiologically strong, causality has not been definitively established due to confounding factors in observational studies 8
• The number needed to harm is higher for the general population (range: 899-3925) compared to hospitalized patients not on antibiotics (range: 202-367) or hospitalized patients on antibiotics (range: 28-50) 1
• PPI use is associated with CDI in both adult and pediatric populations 3
• Dose-response analyses show increasing PPI exposure correlates with increased CDI risk (OR=1.65 per prescription increase) 4