Khanna, Sahil

Background: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. Methods: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. Results: Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) ( n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given ( p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days ( p = 0.02) and at 90 days ( p = 0.009). Conclusion: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results.

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: Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis. Aim: The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI). Methods: We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I 2 >50%. Results: From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I 2 =96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P >0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias. Conclusions: Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.

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.

Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed.

AbstractClostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare‐associated infection, and its management is a clinical conundrum. Over 450 000 infections are seen in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild–moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2‐step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C. difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule‐based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER‐109 (positive phase III results) and VE303 (ongoing phase II trial). Enema‐based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.