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

Abstract

Abstract 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.