An Open-Label Study (ECOSPOR IV) to Evaluate the Safety, Efficacy and Durability of SER-109, an Investigational Oral Microbiome Therapeutic, in Adults With Recurrent Clostridioides difficile Infection (rCDI)

The rate of rCDI was low and durable, regardless of the number of prior episodes, supporting the potential benefit of microbiome repair following antibiotics for rCDI. Summary of Treatment-Emergent Adverse Events Within 8 Weeks After Treatment, Safety Population Cohort 1 Cohort 2 (N=234) n (%) Total (N=263) n (%) Randomized Treatment Arm in ECOSPOR III Total (N=29) n (%) SER-109 (N=4) n (%) Placebo (N=25) n (%) Any TEAE 4 (100.0) 15 (60.0) 19 (65.5) 118 (50.4) 137 (52.1) Most Frequently Reported TEAEs by Preferred Term (≥5% in any cohort)  Diarrhoea 1 (25.0) 9 (36.0) 10 (34.5) 49 (20.9) 59 (22.4)  Flatulence 0 4 (16.0) 4 (13.8) 16 (6.8) 20 (7.6)  Nausea 0 3 (12.0) 3 (10.3) 17 (7.3) 20 (7.6)  Abdominal pain 1 (25.0) 2 (8.0) 3 (10.3) 15 (6.4) 18 (6.8)  Fatigue 0 3 (12.0) 3 (10.3) 9 (3.8) 12 (4.6)  Urinary tract infection 0 0 0 12 (5.1) 12 (4.6)  Abdominal distension 1 (25.0) 3 (12.0) 4 (13.8) 7 (3.0) 11 (4.2) Related/Possibly Related TEAE 1 (25.0) 4 (16.0) 5 (17.2) 27 (11.5) 32 (12.2) Severe TEAEs 0 1 (4.0) 1 (3.4) 18 (7.7) 19 (7.2) Serious TEAEs 0 0 0 20 (8.5) 20 (7.6) Serious TEAEs Related/Possibly Related to Study Drug 0 0 0 0 0 Treatment-emergent AESIs 0 0 0 10 (4.3) 10 (3.8) TEAEs Leading to Death1 0 0 0 6 (2.6) 6 (2.3) Abbreviations: AESI = adverse event of special interest;TEAE = treatment-emergent adverse event Notes: Data presented are by subject. All TEAEs were collected and summarized from time of enrollment up to Week 8;Note: N is number of subjects in the Safety Population who are in the study at the beginning of the specified time interval. 1 TEAEs leading to death by preferred term included: congestive cardiomyopathy (1 subject), coronavirus infection and intestinal peforation (1 subect), death due to natural causes (1 subject), clostridium difficile infection (1 subject), necrotising fasciitis (1 subject), and pancreatic carcinoma (1 subject).

Microscopic colitis: Etiopathology, diagnosis, and rational management.

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations.

OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic. METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19. RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted. CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.

Outcomes in Patients with SARS-CoV-2 and Clostridioides difficile Coinfection.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is primarily a respiratory disease. However, it may manifest with gastrointestinal symptoms that may overlap with Clostridioides difficile infection (CDI). COVID-19 appears to have higher mortality in those with comorbidities. We aimed to assess the outcomes of coinfection in these patients. METHODS: A retrospective chart review was conducted to identify patients with CDI and COVID-19 from January 1st, 2020 to November 17th, 2020. Both infections were diagnosed via PCR. Clinical features, treatment for COVID-19 and CDI and outcomes including intensive care unit admission, colectomy, 30 day-mortality and long-term complications were analyzed. RESULTS: Overall, 21 patients (20 hospitalized) with median age 70.9 years (range 51.8-90.7 years) had CDI and COVID-19 within 4 weeks of each other. Of these, 4 patients (19%) with CDI were diagnosed with COVID-19 at the time of admission, 12 (57%) had CDI diagnosed after COVID-19, and 5 (23.9%) developed COVID-19 within 4 weeks after CDI. Fourteen patients (66.7%) were treated with medications directed against COVID-19 including remdesivir and dexamethasone (n=7), remdesivir with convalescent plasma (n= 1), remdesivir (n= 5) and dexamethasone (n=1). The most common treatment for CDI was oral vancomycin in 20 patients (95.2%), and 1 patient received intravenous metronidazole. No patient required colectomy for CDI but 2 (9.5%) required ICU admission. Four patients (19%) died likely due to COVID-19 with median age 80 years (range 61-90 years). CONCLUSION: The relationship between COVID-19 and CDI is poorly understood, and studies are required to further investigate this association. Whether coinfection results in a worsening of outcomes, including mortality and clinical course, are questions that should be answered in future research studies. Diagnosing both infections for appropriate management is vital in light of overlapping symptoms.

Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A Systematic Review and Meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the prevalence of gastrointestinal (GI) symptoms and mortality in patients with coronavirus disease 2019 (COVID-19) diagnosed. METHODS: A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed from December 1, 2019 to May 7, 2020. Observational studies including adults with COVID-19 infection and reporting GI symptoms were included. The primary outcome was assessing the weighted pooled prevalence (WPP) of GI symptoms in patients with COVID-19 infection. Secondary outcomes were WPP of overall mortality, and mortality in patients with COVID-19 infection with GI symptoms. RESULTS: A total of 78 studies with 12,797 patients were included. Among GI symptoms (at onset of illness in 6, at admission in 17, data given separately for both in 3, and data unavailable in 52 studies), the WPP of diarrhea was 12.4% (95% CI, 8.2% to 17.1%), I2=94%; nausea and/or vomiting, 9.0% (95% CI, 5.5% to 12.9%), I2=93%; loss of appetite, 22.3% (95% CI, 11.2% to 34.6%, I2=94%; and abdominal pain, 6.2% (95% CI, 2.6% to 10.3%), I2=92%. Mortality among patients with GI symptoms (0.4%; 95% CI, 0% to 1.1%; I2=74%) was similar to overall mortality (2.1%; 95% CI, 0.2% to 4.7%; I2=94%), P=.15. Most studies had high risk of bias and overall quality of evidence was low to very low for all outcomes. CONCLUSION: Gastrointestinal symptoms are seen in up to 1 in 5 patients with COVID-19 infection. More high-quality evidence is needed to confirm these findings and explore factors causing mortality in these patients.