Sehgal, Kanika

Background: Clostridioides difficile infection (CDI) treated with bezlotoxumab (BEZ) has been demonstrated to have a lower recurrence rate than placebo in clinical trials. However, real-world data on BEZ’s effectiveness remain limited and heterogeneous. Objectives: To evaluate the real-world effectiveness of BEZ in preventing CDI recurrence through a single-center retrospective cohort and a meta-analysis. Design: A retrospective cohort study and a meta-analysis. Methods: A retrospective study of patients treated with BEZ from 2017 to 2021 was performed at the Mayo Clinic. Demographics, CDI diagnostics, and several prespecified risk factors were analyzed. A literature search was conducted in August 2024 utilizing the Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science Core Collection. Studies reporting CDI resolution rates with BEZ were included. The random-effects model described by DerSimonian and Laird was used to calculate weighted pooled resolution rates (WPR) with 95% confidence intervals (CI). We assessed heterogeneity with the inconsistency index ( I 2 ) statistic. Results: Across 28 studies and our retrospective cohort, 2639 CDI patients were analyzed. Among 1786 patients treated with BEZ, 1450 achieved clinical resolution (WPR: 81.6%, 95% CI 77.2–85.6%), with significant heterogeneity ( I ² = 77.3%). In subgroup analysis, the pooled relative risk of recurrence was 0.56 (95% CI 0.36–0.88; p < 0.01) for BEZ with SoC compared to SoC alone. A WPR of 83.3% (95% CI 75.5%–91.1%) for patients receiving BEZ with SoC was observed when compared with a WPR of 70.8% (95% CI 62.7%–78.8%) in patients receiving SoC alone on subgroup analysis. In our cohort of 47 patients, the CDI resolution rate was 72.3% (34/47). Conclusion: Our retrospective study and meta-analysis demonstrate the real-world efficacy of BEZ in reducing CDI recurrence. The higher recurrence rates in our cohort likely reflect the high-risk nature of the population, including a greater proportion of immunocompromised patients.

Background: Fecal microbiota transplantation (FMT) is a successful therapy for Clostridioides difficile infection (CDI). FMT from overweight donors is speculated to influence the recipient’s body mass index (BMI) after administration for CDI. Objectives: We investigated changes in the recipient’s BMI after FMT in relation to the donor’s BMI. Design: We conducted a retrospective cohort study involving patients who underwent FMT for recurrent CDI at Mayo Clinic between 2012 and 2019. Methods: We analyzed demographic and donor data for patients undergoing FMT at Mayo Clinic (2012–2019). Recipient BMI (pre- and post-FMT) and donor BMI were extracted from medical records. Mixed-effects linear regression was used to evaluate the impact of donor BMI, donor BMI category, recipient baseline BMI, time before and after FMT, and interactions between these variables on overall BMI change and BMI change per month. Kaplan–Meier curves were used to assess BMI changes (⩾5 units) based on the last recorded post-FMT BMI. Results: We analyzed data from 401 patients with recorded BMI measurements before and after FMT. The median age of the recipients at the time of FMT was 59.1 years (interquartile range (IQR): 40.5–70.1 years), with 61.6% being female. The median BMI for recipients prior to FMT was 26.7 kg/m² (IQR: 22.7–31.6 kg/m²), while the median BMI of the donors was 24.5 kg/m2 (IQR: 23.9–27.5 kg/m2). Stool from donors with a normal BMI was used for 58.2% of recipients, while 41.8% received stool from pre-obese donors. Donor BMI data were missing for 3.2% of recipients. Donor BMI was not significantly associated with changes in recipient BMI; for each 1-unit increase in donor BMI, a 0.01-unit monthly increase was observed (95% confidence interval: −0.0003, 0.02; p = 0.11). The log-rank test for BMI increases (⩾+5) and decreases (⩽−5) revealed no significant differences among the donor BMI groups (Chi-squared = 4.4, p = 0.1 for increases, Chi-squared = 2, p = 0.4 for decreases). Conclusion: The lack of impact of donor BMI on BMI changes post-FMT suggests that these changes are more dependent on the recipient’s metabolic profile. Prospective, controlled trials are required to analyze these results more comprehensively.

Introduction Hospitalizations, proton-pump inhibitors (PPI), and systemic antibiotics increase the risk of Clostridioides difficile infection (CDI) in cirrhosis. We compare the risk of CDI with hepatic encephalopathy (HE) medications, hypothesizing that rifaximin may decrease CDI risk. Materials and Methods A retrospective study of hospitalized HE patients treated with lactulose and/or rifaximin at Mayo Clinic Minnesota, Florida, and Arizona from 2008 to 2013 was conducted. Data on demographics, hospitalizations, antibiotics, and PPI use and CDI were gathered. Univariate and multivariable cox models were constructed. Results We found 1,112 hospitalizations in 1,055 unique patients (55 had 1 subsequent readmission, 1 patient had 2); 428 (40.6%) patients were women (median age: 58 years [interquartile range: 52–65]). CDI developed after 66/1,112 (5.9%) hospitalizations within 12 months post-discharge. Lactulose was administered in 21 (31.8%), rifaximin in 5 (7.6%), both in 40 (60.6%) hospitalizations. Systemic antibiotics were used in 28 (42.4%) patients and PPIs in 60 (90.9%) patients.Univariate analysis using medication (with lactulose alone as the reference group) showed rifaximin was not significantly associated with CDI compared with lactulose (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 0.57–4.33, p = 0.39). Use of both medications was not significant compared with lactulose (HR: 1.41, 95% CI: 0.84–2.38, p = 0.19). Results were similar after controlling for confounders. Multivariable analysis based on length of stay, age, and gender showed no differences between rifaximin versus lactulose and both versus lactulose. Conclusion There is no significant difference between lactulose and rifaximin on CDI development in HE patients. However, CDI should still be considered when managing diarrhea in HE patients.

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34–3.31, p = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34–3.02, p = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16–3.00, p = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19–0.83, p = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14–0.42, p < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47–1.05, p = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide.

INTRODUCTION: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known. METHODS: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002–2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years). RESULTS: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23–91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3–18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts. DISCUSSION: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.