The pathogenesis of Clostridioides difficile infection (CDI) was recognized with its link to the use of antimicrobials. Antimicrobials significantly alter gut microbiota structure and composition, which led to the discovery of the association of this gut perturbation with the development of CDI. A number of factors implicated in its pathogenesis, such as advancing age, proton-pump inhibitors, and gastrointestinal diseases, are linked to gut microbiota perturbations. In an effort to better understand CDI, a multitude of studies have tried to ascertain protective and predictive microbial footprints linked with CDI. It has further been realized that CDI in itself can alter the gut microbiome. Its spore-forming capability poses as an impediment in the management of the infection and contributes to its recurrence. Antibiotic therapies used for its management have also been linked to gut microbiota changes, making its treatment a little more challenging. In an effort to exploit and utilize this association, gut microbial restoration therapies, particularly in the form of fecal microbial transplant, are increasingly being put to use and are proving to be beneficial. In this review, we summarize the association of the gut microbiome and microbial perturbation with initial and recurrent CDI.

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

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.

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The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins – A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection.