Calcineurin inhibitors may significantly increase the risk of community-acquired Clostridioides difficile infection, according to study results published in Clinical Infectious Diseases. These results also suggest that the greatest risk of infection is found among patients taking multiple classes of immunosuppressants.

Although exposure to immunosuppressants is associated with an increased risk of developing C difficile infection, the extent of the risks across immunosuppressant classes is not well understood. A team of investigators conducted a retrospective study to better understand whether there is an equally shared risk for C difficile infection across immunosuppressant classes.

Electronic health records were obtained from adults who were hospitalized from 2010 to 2019 and tested for community-acquired C difficile infection within 72 hours of hospital admission. The primary outcome was a positive test for community-acquired C difficile infection. The primary exposure was immunosuppressant use at home, which was further categorized by classes including systemic steroids, calcineurin inhibitors, antimetabolites, anti-TNFα agents, anti-CD20 antibody, and all other classes.


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Of the 10,992 patients included in the analysis, 1795 (16%) had C difficile infection. A greater number of patients with C difficile infection used immunosuppressants compared with patients who did not have C difficile infection (27% vs 22%, respectively; P <.01). 

Patients with C difficile infection were also more likely than patients without C difficile infection to have comorbidities, have previous hospitalizations, and use proton pump inhibitors.

More patients with C difficile infection were treated with antibiotics compared with patients who did not have C difficile infection (78% vs 73%, respectively; P <.01).

Of the cohort, 23% of patients used 1 or more classes of immunosuppressants, the most common of which were systemic steroids (16%), calcineurin inhibitors (14%), and antimetabolites (10%). However, the greatest crude risk for community-acquired C difficile infection was found in patients taking calcineurin inhibitors (21%) or antimetabolites (21%), followed by systemic steroids (20%). After adjustment for demographics and other clinical characteristics, increased risk for community-acquired C difficile infection was associated with only calcineurin inhibitors (adjusted odds ratio, 1.19).

In a sensitivity analysis, the use of multiple immunosuppressant classes was associated with an increased risk for community-acquired C difficile infection, with adjusted odds ratios of 1.22, 1.53, and 2.40 for the use of 2, 3, and 4 or more classes of immunosuppressants, respectively.

These data suggest “that the risk for [community-acquired C difficile infection] serious enough to require hospitalization associated with immunosuppression may be lower than is generally perceived, and also that not all immunosuppressants are equal in regards to risk for [C difficile infection],” the study authors noted. “A more comprehensive understanding of the relationship between immunosuppressant class and [community-acquired C difficile infection] may inform [C difficile infection] testing and also future strategies seeking to target high-risk populations for prevention.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Varma S, Greendyke WG, Li J, Freedberg DE. Class-specific relationship between use of immunosuppressants and risk for community-acquired Clostridioides difficile infection. Clin Infect Dis. Published online June 22, 2021. doi:10.1093/cid/ciab567