Analysis of the impact of secondary prophylaxis onClostridioides difficilerecurrence in critically ill adults

Introduction: Clostridioides(formerlyClostridium)difficileinfection recurrence in patients re-exposed to antibiotics for treatment of a non-Clostridioides difficileinfection is high at approximately 33%. Low-dose per os vancomycin (e.g. 125 mg q12 h) or metronidazole (e.g. 500 mg intravenous/per osq8 h) may help prevent recurrences, but study of secondary prophylaxis in critically ill patients is needed. Objectives: To determine whether critically ill adults receiving low-dose per os vancomycin for secondaryClostridioides difficileinfection prophylaxis have fewer recurrences ofClostridioides difficileinfection in 90 days compared with patients receiving metronidazole for secondaryClostridioides difficileinfection prophylaxis or control (no secondary prophylaxis). Methods: This was a retrospective, two-center, observational study in a large academic medical center and affiliated community hospital. Included patients had a history ofClostridioides difficileinfection within 1 year of receiving antibiotics for clinical care. We compared patients receiving secondary prophylaxis with vancomycin or metronidazole and control patients; in addition, an unplanned fourth group (vancomycin/metronidazole combination) was identified and analyzed. The primary outcome wasClostridioides difficileinfection recurrence within 90 days of a course of broad-spectrum antibiotic therapy. Fisher's exact, analysis of variance, and Kruskal-Wallis tests were used to compareClostridioides difficileinfection recurrence with prophylaxis group and additional contributing factors. Results: Eighty-two patients were included: 38 control (46.3%), 20 metronidazole (24.4%), 17 vancomycin (20.7%), and 7 combination (8.5%). Ten of 82 patients (12.2%) had at least oneClostridioides difficileinfection recurrence; 8/38 patients in the control group (21.1%), 1/7 patients in the combination group (14.3%), 1/17 patients in the per os vancomycin group (5.9%), and 0/20 in the metronidazole group (0%; p = 0.073). As a post hoc secondary analysis, the three prophylaxis groups were coalesced into one group and compared with control (4.5% vs 21%; p = 0.039). Additional factors (e.g. age, obesity, immunosuppression, acid suppression) were not significantly associated withClostridioides difficileinfection recurrence or with prophylaxis group. Conclusion: There was no difference inClostridioides difficileinfection recurrence between prophylaxis groups, however, given the low recurrence rate, prospective evaluation with a larger sample of critically ill patients is necessary.