Multicenter retrospective study demonstrates probiotics may increase CDI recurrence in severe cases, suggesting caution in use.
Background Clostridioides difficile infection (CDI) is a major healthcare burden, particularly in severe cases with high recurrence and mortality rates. Probiotics are often used alongside antibiotics to restore gut microbiota, but their efficacy and safety remain controversial. This study compares outcomes in patients with severe CDI treated with antibiotics alone versus antibiotics plus probiotics. Methods A retrospective cohort analysis was conducted using the TriNetX Research Network. Adult patients (≥18 years) diagnosed with severe CDI between 2010 and 2023 were included. Patients were divided into two cohorts: (1) Antibiotics + Probiotics Group, receiving fidaxomicin, vancomycin, or metronidazole with probiotics (Lactobacillus spp. or Saccharomyces boulardii), and (2) Antibiotics-Only Group, with propensity score matching (1:1) balanced baseline characteristics. Results After matching, 1,146 patients were included in each group, the mean age was (66.3 ± 15.8 vs 66.4 ± 15.1) retrospectively, and female was 47.644% vs 48.429%. At three months, the Antibiotics + Probiotics group had higher risks of CDI recurrence (57.8% vs 44.6%, HR: 1.334, p < 0.0001), diarrhea (23% vs 16%, HR: 1.376, p < 0.0001), MACEs (41.7% vs 33.4%, HR: 1.240, p = 0.0002), and IBD flare-ups (5.1% vs 2.9%, HR: 1.629, p = 0.0072). However, all-cause mortality was lower (11.5% vs 15.3%, HR: 0.685, p = 0.0191). These trends persisted at one year. Conclusion Probiotics were associated with increased recurrent CDI, diarrhea, MACEs, and IBD flare-ups, despite lower mortality. These findings challenge routine probiotic use in severe CDI and highlight the need for targeted, strain-specific trials. Conflict of interest: Hussein, Abdullah: No conflict of interest Rajab, Islam: No conflict of interest Mabrouk, Mohamed: No conflict of interest Nazir, Abubakar: No conflict of interest S. Elgendy, Mohamed: No conflict of interest Altobaishat, Obieda: No conflict of interest ElSafty, Mahmoud: No conflict of interest Bathobakae, Lefika: No conflict of interest Khatib, Elaf: No conflict of interest Patel, Dhruv: No conflict of interest Baddoura, Walid: No conflict of interest
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