| Summary: | Fluoroquinolones are associated with an increased risk of <i>Clostridioides difficile</i> infection (CDI). Probiotic supplementation has been shown to reduce the risk of antibiotic-associated diarrhea with variable effects on CDI. The objective of this study was to evaluate receipt of probiotics on development of primary CDI among hospitalized patients receiving fluoroquinolones. A retrospective cohort was evaluated that consisted of two groups of 100 patients each, admitted August 2018 through August 2020 that received ≥3 days of definitive monotherapy with levofloxacin or ciprofloxacin within 72 h of admission. Primary outcome was incidence of CDI. Secondary outcomes included rates of <i>C. difficile</i> diagnostic stool testing, additional infectious diagnostic testing, and non-CDI related gastrointestinal side effects. Patients on fluoroquinolones who received probiotics had a non-statistically significantly lower incidence in overall cases of CDI compared to those who did not receive probiotics (0% vs. 3%, <i>p</i> = 0.246). Patients who received probiotics had statistically significantly fewer <i>C. difficile</i> diagnostic stool tests performed (4% vs. 16%, <i>p</i> = 0.005) and fewer additional infectious diagnostic testing performed (4% vs. 10%, <i>p</i> = 0.096), respectively. Further research is warranted to optimize and standardize probiotic prescribing in high-risk patients.
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