Can proton pump inhibitors (PPIs) be given to a patient with Clostridioides difficile (C. diff) infection?

Proton Pump Inhibitors in Patients with C. difficile Infection

Proton pump inhibitors (PPIs) should be discontinued in patients with C. difficile infection (CDI) unless there is a compelling clinical indication for their continued use. 1, 2

Risk Association Between PPIs and C. difficile

• PPIs have been epidemiologically associated with an increased risk of C. difficile infection 1
• PPIs can increase the risk of recurrent CDI by approximately 42% 3
• Both oral and intravenous PPI administration routes are independently associated with CDI 4
• The FDA drug label for pantoprazole specifically warns that "PPI therapy may be associated with an increased risk of Clostridium difficile associated diarrhea" 2

Guidelines on PPI Use in CDI Patients

• The 2017 IDSA/SHEA guidelines acknowledge the epidemiologic association between PPI use and CDI but note that there is insufficient evidence for a strong recommendation to discontinue PPIs as a measure for preventing CDI 1
• However, the guidelines emphasize that "unnecessary PPIs should always be discontinued" as part of good stewardship practice 1
• The 2019 World Society of Emergency Surgery (WSES) guidelines similarly state that "stewardship activities to discontinue unneeded PPIs are strongly warranted" 1

Decision-Making Algorithm for PPI Use in CDI Patients

1. Evaluate necessity of PPI therapy:

   • Determine if there is a clear, compelling indication for PPI use (e.g., active peptic ulcer disease, severe GERD, prevention of GI bleeding in high-risk patients) 1
   • If no clear indication exists, discontinue the PPI 1

2. For patients with legitimate PPI indications:

   • Consider the risk-benefit ratio carefully 1
   • Use the minimum effective dose required to treat symptoms 1
   • Consider temporary discontinuation during acute CDI treatment if clinically feasible 1
   • If PPI must be continued, monitor closely for CDI recurrence 3

3. For patients at high risk of CDI recurrence:

   • Exercise extra caution with PPI use in:
     • Elderly patients (>80 years) 3
     • Patients receiving concomitant antibiotics 5
     • Patients with prior CDI episodes 3

Important Clinical Considerations

• The risk of CDI associated with PPI use appears to be higher when fewer antibiotics are used, suggesting a potentially clinically relevant interaction between antibiotics and PPIs 5
• When treating CDI, discontinuing the inciting antibiotic agent(s) as soon as possible is recommended, as continued antibiotic use is significantly associated with increased risk of CDI recurrence 1
• If continued antibiotic therapy is required for treatment of a primary infection, consider using antimicrobials less frequently implicated with CDI (e.g., parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline) 1

Pitfalls to Avoid

• Do not continue PPIs without a clear indication in patients with CDI 1
• Avoid assuming that PPIs are benign medications; they carry multiple potential risks including CDI, bone fractures, hypomagnesemia, and vitamin B12 deficiency 2
• Do not overlook the potential for PPIs to contribute to CDI recurrence, especially in high-risk patients 3
• Remember that both oral and intravenous PPI formulations are associated with increased CDI risk 4