ABSTRACT Background Clostridioides difficile infection (CDI) is a common complication in patients receiving broad‐spectrum antibiotics and causes significant morbidity, especially in solid organ transplant recipients. Oral vancomycin has shown potential for CDI prophylaxis, whereas metronidazole has been used solely for treatment; however, their effectiveness as primary prophylaxis remains uncertain. This study evaluates oral vancomycin or metronidazole prophylaxis in preventing primary CDI among lung transplant recipients (LTRs) during the index transplant admission. Methods We conducted a retrospective chart review of all LTRs at the University of Kentucky from January 2020 to May 2023. Patients were grouped based on whether they received primary CDI prophylaxis (oral vancomycin or metronidazole) during systemic antibiotic therapy at transplant. The primary outcome was the incidence of CDI during the index admission. Secondary outcomes included CDI incidence within 1 year post‐transplant and all‐cause mortality. Results Of 92 LTRs, 51 (55.4%) received prophylaxis and 41 (44.6%) did not. The incidence of CDI during the index admission was 2.0% (1/51) in the prophylaxis group and 2.4% (1/41) in the non‐prophylaxis group. Within 1 year, CDI incidence was 5.9% versus 2.4%, respectively ( p = 0.626). All‐cause mortality was significantly higher in the prophylaxis group (41.2% vs. 19.5%; p = 0.041), likely reflecting greater baseline illness severity and comorbidities. Conclusions Primary prophylaxis with oral vancomycin or metronidazole did not reduce CDI incidence among LTRs. Prophylaxis was more frequently used in patients with prolonged hospitalizations and longer antibiotic courses. Larger studies are needed to clarify the role of primary CDI prophylaxis in this high‐risk population.
Irwin et al. (2026) studied this question.