What is the risk of Clostridioides difficile (C. Diff) infection in patients on chronic trimethoprim?

Risk of C. difficile Infection in Patients on Chronic Trimethoprim

Patients on chronic trimethoprim have a significant risk of developing Clostridioides difficile infection, though this risk is lower compared to other antibiotics such as clindamycin, fluoroquinolones, and cephalosporins. 1, 2

Risk Assessment of Trimethoprim for C. difficile Infection

• Trimethoprim, like all antibiotics, can disrupt the normal gut microbiota, creating conditions favorable for C. difficile proliferation and toxin production 1
• According to FDA labeling, C. difficile-associated diarrhea (CDAD) has been reported with the use of trimethoprim and may range in severity from mild diarrhea to fatal colitis 1
• In a 2019 analysis of the FDA Adverse Event Reporting System, trimethoprim-sulfonamides had a significant association with CDI with a Reporting Odds Ratio of 3.32 (95% CI 2.03-5.43) 2
• This risk is considerably lower than that of lincosamides (ROR 46.95), cephalosporins (ROR 15.33), and fluoroquinolones (ROR 4.94) 2

Mechanism of C. difficile Infection Risk with Antibiotics

• Treatment with antibiotics alters the normal flora of the colon leading to overgrowth of C. difficile 1
• C. difficile produces toxins A and B which contribute to the development of CDAD 1
• The disruption of intestinal microbiota by antibiotics is long-lasting, and the risk of CDI increases both during therapy and in the 3-month period following cessation of therapy 3
• The highest risk of CDI (7- to 10-fold increase) appears to be during and in the first month after antibiotic exposure 3

Risk Factors That May Increase C. difficile Risk in Patients on Trimethoprim

• Advanced age is one of the most important risk factors for CDI 3
• Duration of hospitalization increases risk, as it may be a proxy for duration and degree of exposure to the organism 3
• Exposure to multiple antibiotics significantly increases the risk for CDI 3
• Concomitant use of proton pump inhibitors may further increase the risk of C. difficile infection 3
• Immunosuppression, including patients with HIV/AIDS, cancer chemotherapy, or other immunocompromising conditions 3

Clinical Implications and Monitoring

• CDAD must be considered in all patients who present with diarrhea following antibiotic use, including trimethoprim 1
• CDAD has been reported to occur over two months after the administration of antibiotics, so a careful medical history is necessary 1
• If CDAD is suspected or confirmed in a patient on chronic trimethoprim, the antibiotic may need to be discontinued if not directed against C. difficile 1
• Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated 1

Prevention Strategies for Patients on Chronic Trimethoprim

• Antibiotic stewardship is key for prevention of C. difficile infection 4
• Consider discontinuation of chronic acid suppressive therapy if possible, as this is another modifiable risk factor 4
• Limit the duration of trimethoprim therapy when possible, as both longer exposure to antibiotics and exposure to multiple antibiotics increase the risk for CDI 3
• Monitor patients for diarrhea and other symptoms of CDI, particularly during the first month of treatment and up to three months after discontinuation 3

In conclusion, while chronic trimethoprim use does carry a risk of C. difficile infection, this risk is lower compared to other commonly prescribed antibiotics. Nevertheless, clinicians should remain vigilant for signs of CDI in patients on long-term trimethoprim therapy, particularly those with additional risk factors.