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Rationale: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by inflammation of the gastrointestinal tract. Patients with IBD are susceptible to various complications, including the coexistence of Clostridioides difficile infection (CDI). The incidence of IBD combined with difficile infection is higher in patients with compromised immune function, which can lead to increased mortality., Patient Concerns: A 43-year-old male presented with recurrent episodes of mucus and bloody stools persisting for more than a month without any identifiable triggering factors. Initially, the stool consistency was normal, but it progressively shifted to a loose and watery texture, with up to 8 occurrences daily., Diagnoses: This case underscores the diagnosis of severe UC through colonoscopy and colonic biopsy, along with the supplementary identification of a positive result for Clostridioides difficile in the fecal sample., Interventions: The patient initiated infliximab therapy alongside a full vancomycin course, demonstrating the potential effectiveness of this intervention in managing early-stage ulcerative colitis with concurrent Clostridioides difficile infection., Outcomes: Following the completion of a full vancomycin course, the patient initiated infliximab therapy. The patient was free from significant discomfort, exhibited no fever, and had no mucopurulent bloody stools. A follow-up blood test indicated reduced inflammatory markers compared to the preoperative period, and the stools were normal., Lessons: We illustrate the potential effectiveness of this medication by presenting an in-depth case report of a patient with early-stage UC. The report outlines the patient inclusion of infliximab to better manage UC inflammation alongside an adjunct vancomycin regimen, given the ineffectiveness of mesalazine therapy and the concurrent presence of Clostridium difficile infection. This case prompts consideration of therapeutic approaches for complex UC and contributes to advancing both research and clinical practice. Nonetheless, we should remain attentive to the variations and potential risks unique to each patient in order to formulate personalized treatment strategies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes., (© 2024. Indian Society of Gastroenterology.)

Aims: Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection., Methods and Results: In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed., Conclusions: In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI., Competing Interests: Declaration of competing interest A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. All other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose of Review: Children with inflammatory bowel disease (IBD) are at increased risk of C. difficile infection (CDI) and experience worse outcomes associated with an infection. In this article, we review recent research on the incidence, diagnosis, complications, and treatment options for CDI in children with IBD., Recent Findings: Children with IBD have an elevated incidence of CDI, but their CDI risk does not associate with established risk factors in adults with IBD. Existing testing methodologies are inadequate at differentiating CDI from C. difficile colonization in children with IBD. Fecal microbiota transplantation offers a durable cure for recurrent CDI. CDI remains a frequent occurrence in children with IBD. Careful clinical monitoring should be used to diagnose CDI and patients with co-occurring IBD and CDI require careful surveillance for worse outcomes. Future research should explore the optimal diagnosis and treatment modalities in this unique patient population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Inflammatory bowel disease (IBD) patients are at increased risk of Clostridium difficile infection (CDI), causing significant morbidity and mortality. This study examined CDI's prevalence, predisposing factors, and clinical outcomes in Saudi hospitalized IBD patients., Methods: : A retrospective case-control study was conducted at a tertiary medical city in Riyadh, Saudi Arabia. All Saudi adult patients with IBD, admitted over the preceding four years were identified from the hospital's database. Eligible patients were divided into those with CDI and those without CDI. Binary logistic regression was used to determine the predisposing factors for CDI among admitted IBD patients., Results: During the study period, 95 patients were admitted with IBD. Crohn's disease (CD) was the predominant type (71.6%), whereas 28.4% of the patients were with ulcerative colitis (UC). Only 16 (16.8%) patients had positive CDI. CDI-positive patients tend to have hypertension and previous use of steroids. Patients with UC tend to have a higher risk of CDI than those with CD. Most patients recovered from the CDI (81.3%) with a median time to CDI clearance of 14 days. Three patients (18.8%) had recurrent CDI; among them, one died., Conclusion: The prevalence of CDI in Saudi IBD patients is similar to that reported elsewhere. UC, steroid treatment, and hypertension are risk factors for CDI in IBD patients. Recurrence of CDI in IBD patients is common and associated with a poor prognosis., Competing Interests: None

Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inflammatory bowel disease (IBD) patients are at risk for Clostridioides difficile infection (CDI). The majority of published outcomes data feature medically treated patients. We aimed to analyze outcomes in a large cohort of surgical IBD patients diagnosed with CDI., Methods: All patients with IBD in the ACS NSQIP Colectomy and Proctectomy (2015-2019) modules were identified. The IBD-CDI and IBD cohorts were propensity score weighted on demographic and surgical factors and compared., Results: In the entire unmatched cohort (n = 12,782), 119/0.93% patients were diagnosed with CDI (74.2% Crohn's/25.7% UC/Indeterminate colitis) within 30-days of surgery. After propensity score weighting, IBD-CDI was associated with increased risk of readmission (OR 4.55 [3.09-6.71], p < 0.001), reoperation (3.17 [1.81-5.52], p < 0.001) and any complication (2.16 [1.47-3.17], p < 0.001). Any SSI (2.58 [1.67-3.98]), organ space SSI (2.49 [1.51-4.11], both p < 0.001), prolonged ventilation (4.03 [1.39-11.69],p = 0.01), acute renal failure (15.06 [4.26-53.26],p < 0.001), stroke (12.36 [1.26-121.06],p = 0.03), sepsis (2.4 [1.39-4.15],p = 0.002) and septic shock (3.29 [1.36-7.96],p = 0.008) were also higher in the IBD-CDI cohort. Mean length of stay was increased by 39% in CDI patients., Conclusion: Post colonic resection, IBD-CDI patients have worse outcomes than IBD patients without CDI. These patients represent a particularly vulnerable cohort who require close monitoring for the development of postoperative complications., Competing Interests: Declaration of competing interest Tara M. Connelly MBBCh, FRCS, PhD: No disclosures, Stefan D. Holubar MD, MS, FACS, FASCRS: consulting fees, Shionogi, Takeda, Guidepoint; Funding: Crohn's and Colitis Foundation. Cillian Clancy FRCS, MD: No disclosures, Ju Yong Cheong MBBS, PhD: No disclosures, Xue Jia MD, MPH: No disclosures, Anuradha R. Bhama MD, FACS, FASCRS: No disclosures, Amy Lightner, MD, FACS, FASCRS: No disclosures, Hermann Kessler MD, PhD, FACS, FASCRS: No disclosures, Michael Valente DO, FACS, FASCRS: No disclosures, David Liska, MD, FACS, FASCRS: No disclosures. None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Few studies investigate the influence of inflammatory bowel disease (IBD) on complications following total knee arthroplasty (TKA). Therefore, we compared complications and readmissions frequencies after TKA in patients with Crohn's disease (CD) and ulcerative colitis (UC) to patients without IBD., Methods: A large administrative claims database was used to identify patients who underwent primary TKAs from 2010 to 2019 and had a diagnosis of IBD before TKA. Patients were stratified into two groups: those with CD (n = 8,369) and those with UC (n = 11,347). These patients were compared a control of 1.3 million patients without an IBD diagnosis. Chi-square and unadjusted odds ratios (OR) with 95% confidence intervals (CI) were used to compare complication frequencies. Multivariable logistic regression was used to evaluate independent risk factors for 90-day complications., Results: Compared to patients without IBD, patients with IBD were associated with higher unadjusted 90-day odds for Clostridium difficile infection (CDI) (CD: OR 2.81 [95% CI 2.17 to 3.63]; p < 0.001; UC: OR 3.01 [95% CI 2.43 to 3.72]; p < 0.001) and two-year periprosthetic joint infection (CD: OR 1.34 [95% CI 1.18 to 1.52]; p < 0.001; UC: OR 1.26 [95% CI 1.13 to 1.41]; p < 0.001). After controlling for risk factors like obesity, tobacco use, and diabetes, both types of IBD were associated with higher 90-day odds for CDI and PJI (p < 0.001 for all)., Conclusion: IBD is associated with higher 90-day postoperative CDI and PJI compared with patients without IBD. Providers should consider discussing these risks with patients who have a diagnosis of IBD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RED receives research support from member; Biocomposites, Inc.; CyMedica Orthopedics; DePuy Synthes Product, Inc.; Flexion Therapeutics; Microport Orthopedics, Inc.; Orthofix, Inc.;Patient-Centered Outcomes Research Institute (PCORI); Smith & Nephew; Stryker; Tissue Gene; and United Orthopedic Corporation; and is a board member of the Baltimore City Medical Society All other authors have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is of increasing concern. This study aimed to investigate the molecular epidemiology and antimicrobial susceptibilities of toxigenic C. difficile isolated from IBD patients and to evaluate the risk factors for CDI in IBD population., Methods: Loose or watery stools from IBD patients were tested for glutamate dehydrogenase, C. difficile toxins A&B and anaerobic culture. Toxigenic C. difficile isolates were characterized by multi-locus sequence typing, ribotyping and antimicrobial susceptibility testing., Results: The prevalence of CDI in IBD patients was 13.6% (43/317). The dominant sequence types (STs) were ST35 (20.9%), ST2 (18.6%) and ST37 (16.3%). The most common ribotypes (RTs) were RT 017 (18.6%), RT 012 (14.0%), and RT 220 (14.0%), whereas RT 027 and RT 078 were not detected in this study. All the isolates were susceptible to vancomycin and metronidazole. The multidrug resistance rate of C. difficile RT 017 was higher (p < 0.01) than that of other RT strains. Recent hospitalization, use of corticosteroids and proton pump inhibitors were related to increased risk of CDI in IBD patients; of these, recent hospitalization and proton pump inhibitors use were independent risk factors., Conclusion: Patients with IBD have a relatively high incidence rate of CDI. C. difficile RT 017 is most frequently isolated from IBD patients in this region and warrants more attention to its high resistance rate. Clinicians should pay greater attention to CDI testing in IBD patients with diarrhea to ensure early diagnosis and initiation of effective treatment., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Fecal microbiota transplantation (FMT) is an increasingly employed treatment option for Clostridioides difficile infection (CDI), with growing data supporting its safety and effectiveness in patients with concurrent inflammatory bowel disease (IBD). Given that alterations in the gut microbiome are associated with both ulcerative colitis (UC) and Crohn's disease (CD), the use of FMT for the treatment of IBD itself is another area of active investigation. In this narrative review, we highlight the evidence for use of FMT in the treatment of CDI in patients with IBD, as well as for IBD alone, and provide insight into the future of microbiome therapeutics.

Aims: Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognise. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonised by the organism, in which case diarrhoeal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile-associated colitis from an IBD flare., Methods and Results: We reviewed the clinical, endoscopic and biopsy findings from 50 patients with established IBD and worsening diarrhoea, including 22 with concurrent positive C. difficile stool toxin polymerase chain reaction (PCR) assays and 28 with negative C. difficile assay results. We found that C. difficile-infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell-rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4, 0 and 4%; P = 0.002, P = 0.03 and P = 0.02, respectively)., Conclusions: Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection., (© 2022 John Wiley & Sons Ltd.)

Background: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD., Methods: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained., Results: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up., Conclusions: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Clostridium innocuum (CI) infection can lead to creeping fat in Crohn's disease and is associated with intestinal strictures. At present, no clinical study ever has evaluated the role of CI infection in inflammatory bowel disease (IBD)., Materials and Methods: In this retrospective cohort study, we enrolled hospitalized IBD patients with culture results for both CI and Clostridioides difficile (CD) in a medical center between October 2019 and April 2021. They were divided into the CI (CI+/CD-), control (CI-/CD-), coinfection (CI+/CD+), and CD (CI-/CD+) groups. We analyzed the risk factors, clinical presentations, and outcomes by comparing the CI and control groups., Results: We enrolled a total of 90 patients, including 22, 39, 13, and 16 patients in the CI, control, coinfection, and CD groups. The incidence rates of CI (CI+) and CD (CD+) were 39% (35/90) and 32% (29/90), respectively. We analyzed the differences between CI and control groups. We identified the use of steroid (77.3% vs. 46.2%, P = 0.018) and 5-aminosalicylic acid (90.9% vs. 64.1%, P = 0.022) as risk factors of CI infection. Clinical analysis showed that more patients in CI group presented with bloody stool (77.3% vs. 51.3%, P = 0.046). Although CI group had significantly lower overall occurrence of intraabdominal abscess (0% vs. 17.9%, P = 0.042), it showed a lower clinical remission rate (50% vs. 87.5%, P = 0.044) and higher Mayo score at the end of follow-up (10 points vs. 3 points, P = 0.008) in ulcerative colitis., Conclusions: CI infection may lead to a poorer clinical remission in ulcerative colitis. We should take it into consideration in IBD patents with active inflamamtion or refractory diarrhea with or without CD infection. Precise identification of CI is imperative to guide approproate antimicrobial therapy because of its intrinsic vancomycin resistance nature., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Ltd.)

Clostridioides difficile infection (CDI) in children with inflammatory bowel disease (IBD) can present and manifest differently from the general population with CDI, and it can worsen the underlying disease course. Furthermore, current clinical assays used to test for CDI do not accurately distinguish between true CDI or colonization. This uncertainty leads to difficulty in identifying the etiology and therapy for symptomatic patients with IBD. Improved diagnostic tests, biomarkers, and safe and effective treatment options are greatly needed for this vulnerable population., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Acute exacerbations of inflammatory bowel disease (IBD) may involve enteric pathogen. We aimed to assess the frequency and outcomes of Clostridium difficille toxin (CDT) and non-CDT enteric infections in symptomatic pediatric patients with IBD., Methods: Patients' records were retrospectively searched for disease flares in which stool samples were collected for enteric pathogens. Each patient with a positive sample was matched with a patient with IBD flare and negative samples for analyzing 1-year outcomes following sampling., Results: A total of 618 pediatric patients with IBD [Crohn's disease, n = 439 (71%), mean age at diagnosis 13.0 ± 3.4 years, girls, n = 264 (42.7%)] had 1048 stool samples during the study period (2001-2018). Of 914 bacterial cultures, 40 (4.3%) were positive, 30 (75%) of which, positive for Campylobacter jejuni. Of 393 samples for CDT, 28 (7.1%) were positive while parasitic infection rate was 21/529 (3.9%).Overall, 19 positive C jejuni cases and 19 positive CDT cases with matching controls were examined. During 12 months of follow-up, the mean number of disease flares and emergency room visits was higher among patients with positive CDT (1.5 ± 1.4 vs 0.5 ± 0.9, P = 0.019, 1.3 ± 1.5 vs 0.4 ± 0.8, P = 0.05, respectively) with a numeric increase of surgical interventions (3 vs 0, P = 0.08). There were no significant differences in disease outcomes between patients with C jejuni infections and matched controls., Conclusions: C difficile and C jejuni are the most common enteric infections among pediatric patients with IBD but only clostridial infection was associated with a more severe disease course within 12 months., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals disease-specific patterns. The IBD group shows increased concentrations of markers of inflammation and tissue damage compared with healthy controls, and metabolic changes associate with susceptibility to CDI. In IBD + CDI, we detect both metabolites associated with inflammation/tissue damage and fermentation products produced by C. difficile. The most discriminating metabolite found is isocaproyltaurine, a covalent conjugate of a distinctive C. difficile fermentation product (isocaproate) and an amino acid associated with tissue damage (taurine), which may be useful as a joint marker of the two disease processes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Corticosteroids (CS) therapy to Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) flares may worsen CDI outcomes., Aim: Assess the impact of early CS exposure on outcomes of IBD patients diagnosed with CDI., Methods: Retrospective study of IBD patients admitted with first-time CDI between 2002 and 2018. Comparisons were made based on CS exposure 48 h from admission. Patients were further subdivided to 5 groups based on CS-antibiotics temporal exposure. The primary outcome was all-cause mortality or colectomy within 3 months. Secondary outcomes were colectomy and mortality rates at 1 year, length of stay, readmissions, bacteremia, and diarrhea improvement by day 7/discharge. Cox proportional hazard model and Kaplan-Meier curves were used to assess the effects on survival. Logistic and ordinal regressions were used to assess primary and secondary outcomes., Results: One hundred thirteen patients (64 CD, 46 UC, and 3 IBDU) were included, 82 (72.5%) received early CS. At baseline, CRP was significantly lower and albumin was higher in the group not exposed to early CS. At 3 months, 4 (4.8%) patients required colectomy and 6 (5.8%) died (p = NS). Length of stay was significantly reduced among patients not exposed to early CS. All other endpoints were not associated with CS exposure. In subgroup analysis, the primary outcome was not significantly different among the sub-groups. Mortality rate at 1 year was significantly lower in patients who did not receive antibiotics for CDI., Conclusion: Early CS therapy in IBD patients hospitalized with CDI is not associated with worse clinical outcomes. However, additional prospective research is required.

Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infections (CDIs), suffering from greater morbidity and mortality than the general population. Previous studies have proven the efficacy of oral vancomycin therapy in CDI, but there are no definitive guidelines to treat patients with IBD. We assessed the relationship between the length of vancomycin therapy and rates of CDI recurrence and reinfection in patients with IBD., Methods: We compared rates of CDI recurrence and reinfection in Crohn's disease and ulcerative colitis (UC) patients receiving long-duration (LD) and short-duration (SD) oral vancomycin therapy, defined as 21-42 days and 10-14 days, respectively. Recurrence and reinfection were defined as positive C. difficile toxin assay by polymerase chain reaction within 8 weeks of the end of antibiotic therapy and after 8 weeks of the end of antibiotic therapy, respectively. The Fisher exact test was used to test for significance, and multivariate logistic regression models were constructed to control for other covariables., Results: One hundred thirty-four patients with IBD (57 ulcerative colitis and 77 Crohn's disease) met inclusion criteria. LD vancomycin had a 1.8% incidence of CDI recurrence, compared with 11.7% in the SD vancomycin group (odds ratio = 0.13, P = 0.043). CDI reinfection rates and time to reinfection were not significantly different (LD 14.0% vs SD 16.9%, P = NS). Multivariate logistic regression models showed that treatment with LD vancomycin had lower odds for recurrence than SD vancomycin (odds ratio = 0.03, P = 0.021)., Discussion: LD vancomycin is associated with lower rates of CDI recurrence compared with SD vancomycin therapy. These results will help guide clinical decisions and the development of a prospective trial.

Background / Aims: Clostridium difficile is a Gram-positive, strict anaerobe, spore-forming bacterium. It can cause self-limiting mild diarrhea, severe diarrhea, pseudomembranous colitis, and fatal fulminant colitis. We aimed to investigate the changes in epidemiology and incidence of C. difficile infection in our hospital database., Patients and Methods: Episodes of C. difficile toxin were identified in hospital database, and data such as age, sex, community versus hospital acquisition, intensive care follow-up, current or previous treatments with antibiotics within the past 3 months, medication with proton pump inhibitors, or immunosuppressive therapies were collected., Results: Toxin-positive 78 individuals constituted the patient group. In univariate analyses, independent risk factors for toxin positivity were community versus hospital acquisition [odds ratio (OR), 5.49; 95% confidence interval (CI), 2.52-11.95; P = 0.0001], presence of inflammatory bowel diseases (IBDs) (OR, 21.5; 95% CI, 8.65-53.44; P = 0.0001), proton pump inhibitors' use (OR, 4.53; 95% CI, 1.97-10.43; P = 0.0001), immunosuppressive drug use (OR, 4.1; 95% CI, 2.01-8.3; P = 0.0001), and use of quinolone group of antibiotics (OR, 5.95; 95% CI, 1.92-18.46; P = 0.001). Antibiotic use was a protective risk factor (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01) and presence of IBDs was an independent risk factor (OR, 6.8; 95% CI, 1.5-30.08; P = 0.01) in community-acquired group (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01)., Conclusion: In recent studies, C. difficile infections were demonstrated to be more frequent in younger individuals who did not have a history of hospitalization but had an underlying disease such as IBD. In our study, we showed the change in the epidemiological data with prominence of underlying diseases such as IBDs., Competing Interests: None

Objective: To investigate the clinical features of Clostridium difficile infection (CDI) in hospitalized patients with inflammatory bowel disease (IBD) and to analyze the impact of CDI on IBD., Methods: A prospective study on patients newly diagnosed with IBD was conducted at the IBD center at Sir Run Run Shaw Hospital from March 2015 to May 2016. Stool samples for anaerobic culture and polymerase chain reaction were used to test CDI and to detect the different toxins in the groups. The patients were followed up for 2 years., Results: Altogether 230 patients with IBD were enrolled, including 77 with ulcerative colitis (UC) and 153 with Crohn's disease (CD). The incidence rate of CDI was 13.9% (32/230). Patients with UC were more susceptible to CDI than those with CD (24.7% vs 8.5%, P < 0.01). Among UC patients, a long disease course, prior hospitalization, proton pump inhibitor use, and disease severity were associated with an increased risk of CDI (all P < 0.05). CDI prolonged hospital stay and increased the rate of long-term surgery rate in UC (both P < 0.05). Among patients with CD, CDI increased both short- and long-term surgery rates during the 2-year follow-up (P < 0.05) and increased repeated hospitalization in the follow-up study (odds ratio 2.41, P = 0.02)., Conclusions: A high incidence rate of CDI in patients hospitalized with IBD was related with longer hospital stay and higher surgery rates in our center. Patients with UC are more vulnerable to CDI than those with CD., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The detection of Clostridioides difficile in inflammatory bowel disease (IBD) patients is a common occurrence, in part due to the standard clinical practice of testing for the presence of C. difficile during acute IBD exacerbations. Given the clinical overlap between C. difficile infections and acute IBD exacerbations (ie, increased frequency of loose stools, abdominal pain), it is hard to differentiate C. difficile infections versus colonizations in patients with underlying IBD who test positive for C. difficile. Here, we review the epidemiology, clinical presentation, risk factors, diagnosis, treatment, and outcomes of IBD patients with positive C. difficile tests., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD., Methods: Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence., Results: One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT., Conclusions: Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy., Methods: This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days., Results: A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55)., Conclusions: Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in patients with IBD with RCDI, and the data in pediatrics are limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric patients with IBD., Methods: We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence., Results: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn disease. Median (interquartile range) age was 13 (11-14) years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 (40-139) days. Two patients (25%) who developed recurrence went to colectomy after FMT., Conclusions: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of C difficile infection after 60 days in these patients.

Background and Aims: Clostridium difficile infection (CDI) incidence and risk factors in patients with inflammatory bowel disease (IBD) have been extensively studied. However, data describing CDI in Chinese patients with IBD are limited. We investigated the cumulative incidence, risk factors, and outcomes of CDI in Chinese IBD patients., Methods: We conducted a retrospective, case-control study of patients hospitalized with IBD and CDI at Peking Union Medical College Hospital from January 2010 to December 2015. CDI was diagnosed based on the presence of active symptoms and positive enzyme immunoassay-based stool test results for C. difficile toxin A or B (CDAB). Controls were selected from CDAB-negative patients with IBD and matched by age, gender, phenotypes of IBD and the same time period of CDAB testing at a 1:2 or 1:3 ratio., Results: We identified 60 (7.41%) cases of CDI among 810 patients with IBD, and 137 control cases were selected. Univariate analysis revealed that IBD patients with CDI had higher rates of concurrent corticosteroid use, proton pump inhibitor, antibiotic use, recent hospitalization, parenteral nutrition support, and cytomegalovirus (CMV) coinfection (P < 0.05). Multivariate analysis revealed that concurrent corticosteroid use (odds ratio [OR] = 6.803, 95% confidence interval [CI] = 2.901-15.954, P < 0.001) and hospitalization within 1 month (OR = 3.028, 95% CI = 1.225-7.480, P = 0.016) were associated with CDI. CMV and C. difficile coinfection (hazard ratio [HR] = 4.185, 95% CI = 1.492-11.736, P = 0.007) as well as disease severity (HR 2.070, 95% CI = 1.006-4.261, P = 0.048) were independently associated with colectomy following CDI., Conclusions: IBD patients with concurrent corticosteroid use and recent hospitalization are at a higher risk of CDI. CMV and C. difficile coinfection is associated with poorer outcomes.

Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients., Competing Interests: Andreas Stallmach weist in Bezugnahme auf das Manuskript folgende Tätigkeiten aus: Beratungstätigkeiten in den letzten drei Jahren für: Astellas, MSD, Summit Therapeutics; Vortragshonorare und Reisekostenerstattung: Astellas, MSD.Philipp Reuken gibt keine Interessenkonflikte an.Niels Teich weist in Bezugnahme auf das Manuskript folgende Tätigkeiten aus: Beratungstätigkeit, Vortragshonorare und Reisekostenerstattungen von MSD., (© Georg Thieme Verlag KG Stuttgart · New York.)

Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012-June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥ 1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6-27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥ 1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.

Objective: Characterization of predisposing factors for Clostridium difficile infection recurrence (rCDI) and outcome in inflammatory bowel disease (IBD) patients., Methods: Clinical characteristics of 167 inflammatory bowel disease patients with Clostridium difficile infection (IBD-CDI cohort) treated in Helsinki University Central Hospital were gathered. Medical history of the last three months preceding a toxin positive CDI test was recorded. Parameters, including ribotype of C. difficile, mortality and recurrence were compared with age and gender-matched C. difficile patients (CDI cohort)., Results: No difference was found in rCDI between IBD-CDI and CDI cohorts. As compared with IBD subtypes, rCDI was least common among patients with Crohn's disease. The use of immunosuppressant therapy was higher in IBD patients with two or more CDI episodes. C. difficile ribotype 027 increased the rates for rCDI in IBD patients but not in non-IBD-CDI patients. The prevalence of 027 ribotype and mortality rates did not differ significantly among the cohorts. None of the IBD patients underwent colectomy upon CDI., Conclusion: IBD patients are not more susceptible for rCDI than non-IBD patients. Predisposing factors for rCDI among IBD patients are associated with immunosuppressant treatments, colon affecting IBD and CDI caused by ribotype 027. CDI does not worsen the prognosis of IBD patients.

Background: Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases., Methods: We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created., Results: No CDI occurs in healthy control mice, wherease the incidence of CDI in IBD mice is 40%; however, in IBD mice that received antibiotics, the incidence of CDI is 100% and the disease is accompanied by high levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone, those IBD mice infected with C. difficile have more severe symptoms, toxemia, histopathological damage, and higher mortality. Moreover, several proinflammatory cytokines and chemokines are significantly elevated in the colon tissues from IBD mice infected with C. difficile., Conclusions: We, for the first time, demonstrate in an animal model that mice with dextran sulfate sodium induced-inflammatory bowel disease are significantly more susceptible to C. difficile infection, and that the bacterial infection led to more severe disease and death. These findings are consistent with clinical observations, thus, the animal model will permit us to study the pathogenesis of these concurrent diseases and to develop therapeutic strategies against the comorbidity of IBD and CDI.

Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. Intestinal microbiota composition in IBD patients with CDI has not been specifically evaluated to date. The fecal microbiota of 56 IBD patients, including 8 in flare with concomitant CDI, 24 in flare without CDI, and 24 in remission, as well as 24 healthy subjects, was studied using 16S sequencing. Analysis was performed using the Qiime pipeline. Compared to IBD patients without CDI, IBD patients with CDI had more pronounced dysbiosis with higher levels of Ruminococcus gnavus and Enterococcus operational taxonomic units (OTUs) and lower levels of Blautia and Dorea OTUs. Correlation network analysis suggested a disrupted ecosystem in IBD patients in flare, particularly in those with CDI. In patients with IBD, CDI is associated with a more pronounced intestinal dysbiosis with specific alterations in intestinal microorganisms.

Background: Interestingly, Clostridium difficile infection (CDI) worsens the course of inflammatory bowel disease (IBD); however, there is a paucity of data regarding the treatment of CDI in this group of patients., Methods: This was a prospective, single-blind trial. Children with flare of IBD and CDI were randomly assigned to receive metronidazole or rifaximin orally for 14 days. CDI was diagnosed based on a positive well-type enzyme immunoassay (EIA) toxins A/B stool test for C. difficile toxins A and/or B. The cure rate was defined as the percentage of patients with a negative EIA stool test for C. difficile toxins A/B measured 4 weeks after the end of treatment. Recurrence was defined as a repeat CDI within 2 to 8 weeks., Results: In total, we included 31 patients with IBD including 12 patients with Crohn's disease and 19 with ulcerative colitis. Of them, 17 received metronidazole and 14 received rifaximin. There were no statistically significant differences between the 2 study groups including age, type of treatment, and disease activity. There was no statistically significant difference in the cure rate between patients treated with metronidazole and rifaximin (70.6% versus 78.6%, respectively, P = 0.5). We found no difference in recurrence rate between the 2 study treatment types (17% versus 0%, respectively, P = 0.3). We did not find an association between immunosuppressive therapy and CDI cure rate or CDI recurrence rate., Conclusions: Metronidazole and rifaximin were similarly effective treatments for CDI in pediatric patients with IBD.

Background: Patients with inflammatory bowel disease are at an increased risk of Clostridium difficile infection (CDI), but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a matched cohort of patients with inflammatory bowel disease., Methods: Patients who tested positive for infection formed the CDI-positive group. We generated a 1:2 propensity matched case to control cohort based on risk factors for CDI in the year before infection. Health care utilization data (emergency department use, hospitalizations, and telephone encounters), medications, laboratories, disease activity, and quality-of-life metrics were compared by CDI status., Results: A total of 198 patients (66 CDI and 132 matched controls) were included (56.6% women; 60.1% Crohn's disease, and 39.9% ulcerative colitis). In the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, low vitamin D, increased disease activity, worse quality of life, and increased health care utilization (all P < 0.01). During the next year after infection, patients with CDI continued to have increased exposure to CDI-targeted antibiotics (P < 0.001) and other antibiotics (P = 0.02). They also continued to have more clinic visits (P = 0.02), telephone encounters (P = 0.001), and increased health care financial charges (P = 0.001)., Conclusions: CDI in inflammatory bowel disease is significantly associated with markers of disease severity, increased health care utilization and poor quality of life during the year of infection, and a 5-fold increase in health care charges in the year after infection (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B658).

The most recent nationwide data show a rising incidence of Clostridium difficile infection in hospitalized patients with ulcerative colitis (UC). We describe recent national trends with regard to incidence, mortality, and the rate of total colectomy. The Nationwide Inpatient Sample database identified patients admitted to hospitals in the United States with diagnoses of C. difficile and inflammatory bowel disease (IBD) during the study years 2007 to 2013. We analyzed incidence of C. difficile, mortality, and colectomy rates. From 2007 to 2013, incidence of patients with IBD admitted with the primary diagnosis of C. difficile rose faster than the non-IBD population (1.24% to 2.14% vs 0.26% to 0.30%, P < 0.0001) and specifically in the UC population rose from 2.36 to 3.48 per cent (P < 0.001). The mortality of non-IBD patients with C. difficile decreased 47 per cent (3.76% to 1.99%, P = 0.003), whereas mortality of IBD patients with C. difficile decreased 54 per cent (6.08% to 2.79%, P = 0.003). For UC patients with primary diagnosis C. difficile, the percentage undergoing total colectomy decreased by 38 per cent (2.47% vs 1.51%, P = 0.049). The incidence of C. difficile continues to rise in the both the IBD and non-IBD population. Our study shows decreasing mortality for IBD and non-IBD patients with C. difficile but a greater decrease in mortality for IBD patients.

Background: Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD., Results: There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD., Conclusions: FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

Background: Clostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied., Aim: To perform a systematic review and meta-analysis to assess the impact of CDI on colectomy risk in IBD., Methods: Multiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow-up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale., Results: Twelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short-term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68-2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39-3.76). In contrast, CDI was associated with higher long-term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18-4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19-7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti-microbial therapy., Conclusion: Based on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long- but not short- term., (© 2017 John Wiley & Sons Ltd.)

Objective: Clostridium difficile infection (CDI) may lead to poor outcomes in patients with inflammatory bowel disease (IBD). In this study we aimed to investigate the cumulative incidence, risk factors and outcome of CDI in patients with IBD in a single center in China., Methods: The clinical features and endoscopic profiles of consecutive IBD patients admitted to Ruijin Hospital, Shanghai Jiaotong University School of Medicine between January 2013 and December 2015 were retrospectively analyzed. CDI was diagnosed based on a positive polymerase chain reaction (PCR) stool test., Results: A total of 260 patients with IBD were enrolled, including 176 with Crohn's disease (CD) and 84 with ulcerative colitis (UC). Altogether 13 (5.0%) patients were diagnosed with CDI. The incidence of CDI was 4.0% (7/176) in CD and 7.1% (6/84) in UC, respectively. The endoscopic feature of pseudomembrane was found in four (33.3%) IBD-CDI patients, and pseudomembrane and deep ulcers were significantly correlated with CDI (P < 0.001 and P = 0.006, respectively). Hemoglobin (Hb) <100 g/L was found to be associated with CDI (OR 3.48, 95% CI 1.04-11.61, P = 0.043). Patients in the CDI group showed a higher risk of developing abdominal abscesses than those in the non-CDI group (OR 6.09, 95% CI 1.8-15.2, P = 0.003)., Conclusions: PCR-based fecal test for CDI should be performed in these IBD patients. Hb <100 g/L may be an important risk factor for CDI in IBD. For patients with CDI, antibiotics should be administered promptly to prevent abdominal abscess., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Hospital discharge databases are used to study the epidemiology of Clostridium difficile infections (CDI) among hospitalized patients with inflammatory bowel disease (IBD). CDI in IBD is increasingly important and accurately estimating its occurrence is critical in understanding its comorbidity. There are limited data on the reliability of the International Classification of Diseases 10th revision (ICD-10) (now widely used in North America) CDI code in determining occurrence of CDI among hospitalized patients. We compared the performance of ICD-10 CDI coding to laboratory confirmed CDI diagnoses., Methods: The University of Manitoba IBD Epidemiology Database was used to identify individuals with and without IBD discharged with CDI diagnoses between 07/01/2005 and 3/31/2014. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICD-10 CDI code was compared to laboratory CDI diagnoses recorded in a province wide CDI dataset. Multivariable logistic regression models were performed to test the predictors of diagnostic inaccuracy of ICD-10 CDI code., Results: There were 273 episodes of laboratory confirmed CDI (hospitalized and non-hospitalized) among 7396 individuals with IBD and 536 among 66,297 matched controls. The sensitivity, specificity, PPV and NPV of ICD-10 CDI code in discharge abstracts was 72.8%, 99.6%, 64.1% and 99.7% among those with IBD and 70.8%, 99.9%, 79.0% and 99.9% among those without IBD. Predictors of diagnostic inaccuracy included IBD, older age, increased co-morbidity and earlier years of hospitalization., Conclusions: Identification of CDI using ICD-10 CDI code in hospital discharge abstracts may not identify up to 30% of CDI cases, with worse performance among those with IBD.

The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure., Methods: We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT., Results: Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI., Conclusions: Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Clostridium difficile infection (CDI) affects patients with inflammatory bowel disease (IBD). The aim of this study was to compare humoral response to C. difficile toxins in IBD patients and control outpatients., Methods: We prospectively followed adult IBD patients and control subjects with serum and stool samples obtained at enrollment and during periods of CDI and tested by PCR. Semiquantitative serum levels of IgM, IgG, and IgA to C. difficile toxins A and B were measured., Results: Overall, 119 stool and 117 serum samples were obtained from 150 subjects. Different levels of IgA to toxin A (P = 0.0016) and toxin B (P = 0.0468) were noted between different IBD groups. Toxin A IgA levels were higher in the Crohn's disease group (P = 0.0321) and ileal pouch anal anastomosis (IPAA) group (P = 0.001) compared with the ulcerative colitis (UC) group, and toxin B IgA levels were higher in the IPAA group compared with the UC group (P = 0.0309). There were lower levels of toxin A IgA in IBD patients compared with those in subjects without new CDI (P = 0.0488) and higher levels in IBD patients with compared with those in subjects without CDI history before enrollment (P = 0.016). There were nonsignificant lower toxin A IgG levels in IBD patients compared with those in subjects without prior CDI (P = 0.095) and higher levels in control subjects with a history of CDI compared with IBD patients with prior CDI (P = 0.049)., Conclusions: Patients with UC have lower IgA levels to C. difficile toxins compared with those with Crohn's disease and those after IPAA. Patients with IBD with prior CDI failed to demonstrate any increase in antitoxin IgG. Our findings suggest that IBD patients may benefit from immunization strategies targeting C. difficile toxins.

Background: Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis., Aim: To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD., Methods: Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed., Results: Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients., Conclusions: FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity., (© 2015 John Wiley & Sons Ltd.)

Objectives: Our aim was to characterize the temporal changes in burden that Clostridium difficile infection (CDI) added to the hospital care of children and young adults with inflammatory bowel disease (IBD) in the United States., Methods: Retrospective analysis of annual, nationally representative samples of children and young adults with IBD., Results: There was a 5-fold increase in IBD hospitalizations with CDI from 1997 to 2011 (P for trend <0.01). During the same period, IBD hospitalizations without CDI increased 2-fold (P for trend <0.01). Mean length of stay for IBD hospitalizations with CDI was consistently longer than that for hospitalizations without CDI and did not significantly change over time (P for trend = 0.47). CDI-related total hospital days in the United States rose from 1702 to 10,194 days per million individuals per year from 1997 to 2011 (P for trend <0.01). Children and young adults hospitalized with CDI had a significantly lower odds of colectomy (0.31) compared with those without CDI. Total charges for CDI-related hospitalizations among children and young adults in the United States rose from $8.7 million in 1997 to $68.2 million in 2011., Conclusions: A widening gap in burden has opened between IBD hospitalizations with and without CDI during the last decade and a half. CDI-related hospitalizations are associated with disproportionately longer lengths of stay, more hospital days, and more charges than hospitalizations without CDI over time. Further work within health systems, hospitals, and practices can help us better understand this enlarging gap to improve clinical care for this vulnerable population.

Unlabelled: Recent changes in the epidemiology of Clostridium difficile infection (CDI) include the identification of patients with inflammatory bowel disease (IBD) as a group at risk in comparison to the general population., Aim: To identify the incidence and risk factors for CDI among patients with IBD., Material and Methods: Case-control study of 78 patients diagnosed with IBD, hospitalized at the Iasi Institute of Gastroenterology and Hepatology between January 2012 and -July 2014. Demographic data and clinical characteristics were reviewed for all patients. IBD patients with positive C. difficile toxins A and B tests were matched by sex, age and type of IBD with IBD patients hospitalized in the same period with negative C. difficile toxins tests., Results: Both groups were comparable for baseline characteristics. Of the 78 patients diagnosed with IBD included in the study, C. difficile was detected in 26 patients (33.33%). There was no statistical difference regarding length of hospital stay (10.42 ± 7.34 vs. 8.01 ± 16.14 days, p = 0.129) between the two study groups. Risk factors for CDI in patients with IBD were: ulcerative colitis (OR = 1.90, CI = 1.320-2.720, p = 0.001), use of proton pump inhibitors (OR = 1.57, CI = 1.133-2.032, p = 0.012), previous antibiotic use (OR = 2.3, CI = 1.587-3.332, p < 0.0001), and albumin < 3 g/dl (OR = 1.78, CI = 1.023-5.558, p = 0.038). Immunosuppressive and anti TNF-α treatment were not risk factors for C. difficile development in patients with IBD., Conclusions: CDI in patients with IBD is a serious infection and should be treated aggressively with close clinical follow-up. Ulcerative colitis, previous treatment with antibiotics and proton pump inhibitors represent risk factors for CDI development in patients with IBD.

Background: Clostridium difficile infection is associated with pediatric inflammatory bowel disease (IBD) in several ways. We sought to investigate C. difficile infection in pediatric patients with IBD in comparison with a group of children with celiac disease and to evaluate IBD disease course of C. difficile infected patients., Methods: In this prospective, comparative, multicenter study, 211 pediatric patients with IBD were enrolled from October 2010 to October 2011 and tested for the presence of C. difficile toxins A and B in their stools at 0, 6, and 12 months. During the same study period, stool specimens for C. difficile toxins analysis were collected from 112 children with celiac disease as controls., Results: Clostridium difficile occurrence was significantly higher in patients with IBD compared with patients with celiac disease (7.5% versus 0.8%; P = 0.008). Clostridium difficile was associated with active disease in 71.4% of patients with IBD (P = 0.01). Colonic involvement was found in 85.7% of patients with C. difficile. Antibiotics, proton pump inhibitors, hospitalization, and IBD therapies were not associated with increased C. difficile detection. At 12 months, a higher number of C. difficile-positive patients at the enrollment started immunosuppressant/biological therapy compared with patients without C. difficile (P = 0.01). At 6 and 12 months, patients with C. difficile were more frequently in active disease than patients without C. difficile (P = 0.04; P = 0.08, respectively). Hospitalizations were higher at 6 months in C. difficile group (P = 0.05)., Conclusions: In conclusion, this study demonstrates that pediatric IBD is associated with increased C. difficile detection. Patients with C. difficile tend to have active colonic disease and a more severe disease course.