Class-Specific Relationship Between Use of Immunosuppressants and Risk for Community-Acquired Clostridioides difficile Infection

Use of multiple immunosuppressant classes was associated with substantially increased risk of community-acquired Clostridioides difficile infection (CA-CDI) among hospitalized patients. Regarding class-specific associations, calcineurin inhibitors were associated with a modest, yet increased risk of CA-CDI. Background Immunosuppressant exposure is associated with risk for Clostridioides difficile infection (CDI). It is unknown whether this risk is shared equally across immunosuppressant classes. Methods This was a retrospective cohort study. Adults were included if they were tested for community-acquired CDI (CA-CDI) by stool polymerase chain reaction within 72 hours of hospitalization between 2010 and 2019. The primary outcome was CA-CDI requiring hospitalization, defined as a positive stool test. The primary exposure was use of a home immunosuppressant, at any dose or duration, defined based on the medication reconciliation, and categorized as systemic steroids, calcineurin inhibitors, antimetabolites, anti-tumor necrosis factor-alpha agents, anti-CD20 antibody, and all others. Results A total of 10 992 hospitalized patients met criteria for the study including 1793 (16%) with CA-CDI; 23% used 1 or more immunosuppressant class. Among those immunosuppressed, 27% tested positive for CA-CDI compared with 22% among those who were not immunosuppressed (P < .01). After adjustment, calcineurin inhibitors (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.01-1.44) were associated with increased risk for CA-CDI. Risk for CA-CDI rose with multiple immunosuppressant classes: aOR, 1.22; aOR, 1.53; and aOR, 2.40 for 2, 3, and 4 classes, respectively. After excluding those with solid organ transplant, the relationship between use of calcineurin inhibitors and CDI increased (aOR, 2.21; 95% CI, 1.40-3.49). Conclusions The greatest risk for CA-CDI was observed among patients using multiple classes of immunosuppressants and those using calcineurin inhibitors. Future studies should recognize that CDI risk differs based on immunosuppressant class.