Analysis of the impact of secondary prophylaxis on Clostridioides difficile recurrence in critically ill adults

Abstract

Introduction: Clostridioides (formerly Clostridium) difficile infection recurrence in patients re-exposed to antibiotics for treatment of a non-Clostridioides difficile infection 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 secondary Clostridioides difficile infection prophylaxis have fewer recurrences of Clostridioides difficile infection in 90 days compared with patients receiving metronidazole for secondary Clostridioides difficile infection 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 of Clostridioides difficile infection 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 was Clostridioides difficile infection 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 compare Clostridioides difficile infection 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 one Clostridioides difficile infection 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 with Clostridioides difficile infection recurrence or with prophylaxis group. Conclusion: There was no difference in Clostridioides difficile infection recurrence between prophylaxis groups, however, given the low recurrence rate, prospective evaluation with a larger sample of critically ill patients is necessary.