Class-specific relationship between use of immunosuppressants and risk for community-acquired Clostridioides difficile infection.

BACKGROUND Immunosuppressant exposure is associated with risk for Clostridioides difficile infection (CDI), however it is unknown whether this risk is shared equally across immunosuppressant classes. METHODS This was a retrospective study. Adults were included if they were tested for community acquired CDI (CA-CDI) by stool PCR within 72 hours of hospital admission from 2010 to 2019. The primary outcome was CA-CDI requiring hospitalization, defined as a positive stool PCR test. The primary exposure was immunosuppressant class, at any dose or duration, defined based on the medication reconciliation performed at hospital admission and categorized as systemic steroids, calcineurin inhibitors, antimetabolites, anti-TNFα agents, anti-CD20 antibody, and all others. RESULTS 10,992 hospitalized patients met criteria for the study including 1,793 (16%) with CA-CDI. 23% used one or more class of immunosuppressant. The most common class was systemic steroids (16%), followed by calcineurin inhibitors (14%) and antimetabolites (10%). Among those using any immunosuppressant, 27% tested positive for CA-CDI compared to 22% among those who did not use any immunosuppressant (P<0.01). After adjusting for baseline patient characteristics, only calcineurin inhibitors (aOR 1.19, 95% CI 1.01-1.44) were associated with increased risk for CA-CDI. Risk for CA-CDI rose with multiple classes of immunosuppressant: aOR 1.22, aOR 1.53, and aOR 2.40 for two, three, and four classes respectively. CONCLUSIONS Calcineurin inhibitors were associated with a modest but significantly increased risk of CA-CDI. The greatest risk was observed among patients using multiple classes of immunosuppressants. Future studies should recognize that CDI risk differs based on immunosuppressant class.