Is it safe to order Protonix (pantoprazole) in a patient with colitis or Clostridioides difficile (C. diff) infection?

Proton Pump Inhibitors in Patients with Colitis or C. difficile Infection

Proton pump inhibitors (PPIs) like Protonix (pantoprazole) should be avoided in patients with C. difficile infection (CDI) or colitis when possible, as they are associated with an increased risk of CDI and may worsen existing infection. 1, 2

Risk Association Between PPIs and C. difficile

• PPIs have a clinical association with increased risk of C. difficile-associated diarrhea (CDAD), particularly in hospitalized patients 1, 2
• The FDA label for pantoprazole specifically warns that PPI therapy may be associated with an increased risk of Clostridium difficile-associated diarrhea 1
• Case-control studies have shown that PPI use within the preceding eight weeks was associated with an increased risk of C. difficile diarrhea (odds ratio 2.5,95% CI 1.5-4.2) 3

Recommendations for PPI Use in Patients with CDI

• Although there is a clinical association between PPI use and CDI, no randomized controlled trials have specifically studied the relationship between discontinuing PPIs and the risk of CDI 2
• Current guidelines recommend stewardship activities to discontinue unneeded PPIs in patients at high risk for CDI 2
• The FDA advises that patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated 1

Management Algorithm for PPIs in Patients with Colitis/CDI

1. For patients with active CDI:

   • Discontinue PPIs if not medically necessary 2
   • If PPI therapy must be continued, use the lowest effective dose for the shortest duration possible 1

2. For patients with history of CDI or at high risk:

   • Evaluate the necessity of the PPI therapy 2
   • Consider H2 receptor antagonists as an alternative if acid suppression is needed 2
   • If PPI is absolutely necessary, monitor closely for signs of CDI recurrence 2

3. For patients with non-C. difficile colitis:

   • Assess risk factors for developing CDI (recent antibiotic use, hospitalization, age >65) 2
   • Consider alternative treatments for acid suppression when possible 1

Additional Considerations

• If a patient on PPI therapy develops diarrhea that does not improve, consider CDI as a potential diagnosis 1, 2
• In patients with CDI who require continued antibiotic therapy for other infections, use antibiotics less frequently implicated with CDI (parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline) 2
• The risk of developing pseudomembranous colitis from antibiotics decreases in the following order: fluoroquinolones, cephalosporins, macrolides, penicillins, nitrofurans and chloramphenicol 4

Pitfalls and Caveats

• Pseudomembrane formation (in C. difficile infection) requires neutrophils, so might not be seen if the patient is neutropenic 2
• In patients with severe C. difficile infection, PPI discontinuation alone is unlikely to be sufficient treatment; appropriate antibiotic therapy with oral vancomycin or fidaxomicin is necessary 2, 5
• Loperamide may be given safely in patients with diarrhea before the results of microbiology tests to exclude infection are available, but there are theoretical risks that high-dose loperamide may predispose to toxic dilatation especially in neutropenic patients with C. difficile infection 2

By following these guidelines, clinicians can make informed decisions about the use of PPIs like Protonix in patients with colitis or C. difficile infection, balancing the need for acid suppression against the potential risks of worsening or triggering CDI.