Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Diagnosis and Management of Clostridium difficile Infection

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

e13606 Background: Clostridioides difficile infection (CDI) is frequently seen in patients with cancer. However, information of the features and clinical course of CDI in this specific setting is lacking. Our objective was to describe the clinical picture of CDI in patients with cancer and to compare it with that observed in patients without cancer. Methods: This was an observational cohort study which included all consecutive patients diagnosed of CDI at the Hospital Universitario de Valme (Sevilla, Spain) between January 2014 and October 2020. Recurrence was defined as the reappearance of symptoms of CDI with microbiologic confirmation of toxigenic Clostridioides difficile in the first 8 weeks after the end of CDI treatment according to the Infectious Diseases Society of America criteria. Results: 481 patients had a first episode of CDI during the study period, 102 (21%) had an active neoplasm at CDI diagnosis and 379 (79%) did not had history of active cancer. The proportion of CDI cases in patients with cancer among the total cases of CDI per year was: 2014: 10/70 (17%); 2015: 10/47 (21%); 2016: 17/59 (29%); 2017: 12/80 (15%); 2018: 23/82 (28%); 2019: 16/80 (20%); 2020: 14/73 (19%); p=0.3). When compared with patients without cancer, those with cancer showed differences in: age (68 [58-79] vs 77 [61-84] years; p=0.002); male sex (68 [58-79] vs 77 [61-84]; p=0.002); Charlson comorbidity index > 2 (93 [92%] vs 234 [63%]; p<0.001); nosocomial or healthcare related CDI (90 [88%] vs 275 [72%]; p<0.001); immunosuppression (72 [70%] vs 52 [14%]; p<0.001); hospitalization during the last year (78 [76%] vs 224 [59%]; p=0.001); concomitant use of proton bomb inhibitors (89 [87%] vs 265 [70%]; p=0.001) and concomitant use of antibiotics (45 [45%] vs 125 [33%]; p<0.03). Regarding CDI treatment, 64 (69%), 25 (27%) and 2 (2%) patients in the cancer-group were treated with metronidazole, vancomycin and fidaxomicin, respectively, whereas the corresponding figures in non-cancer patients were 228 (67%), 102 (30%) and 5 (1.5%) (p=0.8). The proportion of oncologic patients receiving vancomycin increased after implementing an antimicrobial stewardship program focused on CDI management during 2017 (2014-2017: 2 [4%]; 2018: 3 (17%); 2019: 11 (73%); 2020: 10 (83%); p<0.001). CDI recurrence could not be assessed in 23 (5%) patients who died during the first 8 weeks of follow-up for reasons other than CDI, including 8 patients with CDI and cancer. Among evaluable patients, 16 (17%) of those with cancer and 61 (17%) of those without cancer had a first CDI recurrence (p=0.9). Conclusions: CDI recurrence rates in cancer patients are similar to that observed in non-cancer patients in spite of a higher frequency of risk factors for recurrence. Appropriate CDI therapy could have counterbalanced this worse profile during recent years. Our study shows that CDI should be included among the scenarios covered by antimicrobial stewardship programs in oncologic patients.

Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI), which can lead to worse IBD outcomes. The diagnosis of CDI in patients with IBD is complicated by higher C. difficile colonization rates and shared clinical symptoms of intestinal inflammation. Traditional risk factors for CDI, such as antibiotic exposure, may be lacking in patients with IBD because of underlying intestinal microbiota dysbiosis. Although CDI disproportionately affects people with IBD, patients with IBD are typically excluded from CDI clinical trials creating a knowledge gap in the diagnosis and management of these 2 diseases. This narrative review aims to provide a comprehensive overview of the diagnosis, treatment, and prevention of CDI in patients with IBD. Distinguishing CDI from C. difficile colonization in the setting of an IBD exacerbation is important to avoid treatment delays. When CDI is diagnosed, extended courses of anti- C. difficile antibiotics may lead to better CDI outcomes. Regardless of a diagnosis of CDI, the presence of C. difficile in a patient with IBD should prompt a disease assessment of the underlying IBD. Microbiota-based therapies and bezlotoxumab seem to be effective in preventing CDI recurrence in patients with IBD. Patients with IBD should be considered at high risk of CDI recurrence and evaluated for a preventative strategy when diagnosed with CDI. Ultimately, the comanagement of CDI in a patient with IBD requires a nuanced, patient-specific approach to distinguish CDI from C. difficile colonization, prevent CDI recurrence, and manage the underlying IBD.

Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.

Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.

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IntroductionAntibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer.MethodsThis non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels.ResultsOn univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05–4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09–6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure.ConclusionUse of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Effectiveness and Safety of Fecal Microbiota Transplantation for Clostridioides Difficile Infection: Results From a 5344-Patient Cohort Study

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at greater risk for development of Clostridioides difficile infection (CDI) than the general population, ulcerative colitis (UC) more so than Crohn's disease (CD). Although the data regarding risk factors for development of CDI in IBD patients is conflicting, a 2019 meta-analysis suggested recent antibiotics, colonic involvement in CD, and biologic therapy to be significant risk factors. This study investigated the role of these risk factors and the use of proton pump inhibitors (PPI), opiates, and steroids in the development of recurrence vs reinfection of CDI in IBD patients. METHODS: A retrospective cohort of patients age 18-75 with a history of IBD diagnosed with CDI from January 1, 2012–December 31, 2016. Recurrence defined as CDI diagnosis within 3 months of the index CDI. Reinfection defined as second episode of CDI between 3 months to 3 years of the index CDI. Patient demographics, antibiotics used to treat index CDI, presence of colonic involvement, and use of PPIs, opiates, biologics, and steroids at the time of second CDI were recorded. Data was analyzed with Fisher's exact test and student t-tests using SAS 9.4 software. RESULTS: A total of 121 IBD patients with CDI were identified: 60 with Crohn's and 61 with UC. 59.5% of IBD patients had either recurrent CDI or CDI reinfection. Recurrent CDI occurred in 32.7% of UC patients and 23.3% of Crohn's patients. CDI reinfection was observed in 36.6% of Crohn's patients and 26.2% of UC patients. Colonic involvement was documented in 100% (n = 14) of Crohn's patients with CDI recurrence and 81.8% (n = 18) of Crohn's patients with CDI reinfection. CDI recurrence and reinfection were not associated with gender, race, or the use of steroids, biologics, PPIs, opiates, or antibiotics. CONCLUSION: Compared to Crohn's patients, there was a greater proportion of UC patients who experienced recurrent CDI. Additionally, colonic involvement occurring in all Crohn's patients in this cohort with recurrent CDI suggests that the extent of colonic disease may predispose to recurrent CDI. Further investigation examining the incidence of recurrent CDI in Crohn's patients without colonic involvement is warranted. This study suggests that therapy with biologics, opiates, PPIs, and steroids are not risk factors for the development of CDI in IBD patients.

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.

Clostridium difficile: A European perspective

Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection

Background: Historically, metronidazole was first-line therapy for Clostridioides difficile infection (CDI). In February 2018, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) updated clinical practice guidelines for CDI. The new guidelines recommend oral vancomycin or fidaxomicin for treatment of initial episode of CDI in adults. We examined the changes in treatment of CDI during 2018 across all types of healthcare settings in metropolitan Atlanta. Methods: Cases were identified through the Georgia Emerging Infections program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in an 8-county area including Atlanta, Georgia (population, 4,126,399). An incident case was a resident of the catchment area with a positive C. difficile toxin test and no additional positive test in the previous 8 weeks. Recurrent CDI was defined as &gt;1 incident CDI episode in 1 year. Clinical and treatment data were abstracted on a random 33% sample of adult (&gt;17 years) cases. Definitive treatment categories were defined as the single antibiotic agent, metronidazole or vancomycin, used to complete a course. We examined the effect of time of infection, location of treatment, and number of CDI episodes on the use of metronidazole only. Results: We analyzed treatment information for 831 adult sampled cases. Overall, cases were treated at 29 hospitals (568 cases), 4 nursing homes (6 cases), and 101 outpatient providers (257 cases). The mean age was 60 (IQR, 34–86), and 111 (13.4%) had recurrent infection. Moreover, ∼28% of first-incident CDI episodes, 8% of second episodes, and 6% of third episodes were treated with metronidazole only. Compared to facility-based providers, outpatient providers were more likely to treat initial CDI episodes with metronidazole only (44% vs 21%; relative risk [RR], 2.1; 95% CI, 1.7–2.7). Treatment changed over time from 56% metronidazole only in January to 10% in December (Fig. 1). First-incident cases in the first quarter of 2018 were more likely to be treated with metronidazole only compared to those in the fourth quarter (RR, 2.76; 95% CI, 1.91–3.97). Conclusions: Preferential use of vancomycin for initial CDI episodes increased throughout 2018 but remained &lt;100%. CDI episodes treated in the outpatient setting and nonrecurrent episodes were more likely to be treated with metronidazole only. Additional studies on persistent barriers to prescribing oral vancomycin, such as cost, are warranted.Funding: NoneDisclosures: Scott Fridkin reports that his spouse receives a consulting fee from the vaccine industry.