Acute severe colitis (ASC) is a relatively frequent manifestation in children with ulcerative colitis and one of the few emergencies in paediatric gastroenterology. A standardized proactive approach based on tight monitoring and timely medical and surgical interventions may improve patients' outcomes. We aimed to update the previous ASC guidelines using detailed recommendations and practice points, based on a systematic review of the literature and consensus of experts. These guidelines update is a joint effort of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organization. A systematic search was performed in Pubmed Ovid Medline, Embase and Cochrane databases using 13 predefined PICO (patient, intervention, comparison, outcomes) based questions and 30 non-PICO based questions. Grading methodology was based on the Oxford Centre for Evidence-Based Medicine-Levels of evidence. The questions were addressed by working subgroups following an iterative consensus voting process, including three online voting meetings and one face-to-face meeting. A total of 36 recommendations and 72 practice points were endorsed with a consensus rate of at least 88% for all statements, regarding initial evaluation, monitoring, medical and surgical treatment of ASC in children. Several topics have been revised since the previous 2018 guidelines and differ from corresponding published adult guidelines. These guidelines present a comprehensive overview of the management of ASC in children, offering practical recommendations and practice points aiming to standardize clinical and surgical treatment and improve outcomes of this severe scenario.

The increasing incidence of Clostridioides difficile infection (CDI) has been associated with poorer prognosis of patients with inflammatory bowel disease (IBD). However, relevant data are limited in China. The aim of this study was to clarify the molecular types and clinical characteristics of C. difficile in IBD patients in China.

Stool samples were collected, cultured anaerobically, and tested for glutamate dehydrogenase and C. difficile toxins A and B. Toxigenic C. difficile isolates were subjected to multi-locus sequence typing and antimicrobial susceptibility testing. Clinical data were collected to compare IBD and non-IBD patients with CDI, and to determine the risk factors associated with CDI in IBD patients.

The incidence of CDI was significantly higher in IBD patients than non-IBD patients (27.2% vs. 9.0%, respectively). Among IBD patients, the dominant sequence types (STs) were ST54 (20.2%), ST2 (14.9%), ST3 (14.9%), and ST42 (13.2%). The STs with the highest multidrug resistance rates were ST37 (100%), ST35 (100%), and ST42 (73.3%). In IBD patients, hospitalization within 6 months and use of 5-aminosalicylic acid were independent risk factors for CDI. Other risk factors included the use of proton pump inhibitors, immunosuppressants, and corticosteroids.

The incidence of CDI was significantly higher in IBD patients than non-IBD patients. Surveillance of CDI in hospitalized patients should be strengthened to reduce the incidence of CDI in IBD patients.

Clostridioides difficile infection (CDI) and acute severe ulcerative colitis (ASUC) are both independently associated with poor outcome. The impact of CDI on the outcome of severe flare of ulcerative colitis is not studied. In the current study, we assess the impact of CDI on the outcome of ASUC.

Data of ASUC patients were collected from January 2022 to July 2024. Parameters included were demographic profile, disease characteristics, biochemical investigations, and stool C. difficile toxin A/B (CDTA). Patients were categorized into ASUC-CDI and ASUC groups. Primary outcomes were need of rescue therapy, colectomy, and mortality during index admission. Six-month outcomes were flare of disease, colectomy, and mortality.

Of the 117 patients included, 91 (77.8%) patients were in the ASUC group and 26 (22.2%) in the ASUC-CDI group. Baseline parameters were similar between the 2 groups. Overall, 86 (73.5%) patients responded to corticosteroid therapy. Need of rescue therapy (24.2% vs. 33.6%, P=0.287), colectomy (3.3% vs. 11.5%, P=0.093), and mortality (1.1% vs. 3.8%, P=0.345) rates were comparable between the ASUC and ASUC-CDI groups. Six-month colectomy (4.4% vs. 15.4%) and mortality (1.1% vs. 7.7%) rates were numerically higher in the ASUC-CDI group, though statistically nonsignificant.

The immediate and short-term outcome of patients with acute severe ulcerative colitis in the presence of C. difficile infection is determined by the severity of ulcerative colitis flare.

The incidence of Clostridium difficile infection (CDI) is increasing around the world, and patients with inflammatory bowel disease (IBD) have a higher risk of obtaining CDI. The data on the incidence rate of CDI in the Asian pediatric IBD population was lacking.

We retrospectively collected data from a tertiary medical center in Taipei, Taiwan. All patients aged 1-18 years old who visited the outpatient department or were admitted to our hospital between 2006 and 2019 were included. CDI was defined as positive stool C. difficile toxin or C. difficile culture results with appropriate antibiotic use within the range of 7 days prior or 14 days after the result.

We compared the average annual incidence of CDI before and after 2013. The average incidence of community-acquired CDI (CA-CDI) increased from 0.063 to 0.564 cases per 1,000 visits, with a rate ratio (RR) of 8.82 (95% CI 5.74-14.38). In patients with IBD, the rate increased from 26.738 to 278.873 cases per 1,000 visits (RR=10.12, 95% CI: 4.57-29.02). The average incidence rate increased from 0.685 to 1.874 cases per 1,000 admissions in pediatric general patients (RR = 2.72, 95% CI 1.82-4.20) and from 14.706 to 62.500 cases per 1,000 admissions in pediatric IBD patients (RR = 3.77, 95% CI 0.71-93.53).

Both CA-CDI and healthcare facility-onset CDI (HO-CDI) were increasing substantially in the pediatric population over the past decade in Taiwan. Compared to the general pediatric population, pediatric IBD patients had a much higher incidence of CDI.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.

Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.

Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.

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.

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.

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.

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.

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.

The prevalence of Clostridium difficile infection (CDI) as a common complication among inflammatory bowel disease (IBD) has been reported to increase worldwide and has been associated with a poor IBD outcome.

In this study, our aim was to report on the prevalence of CDI among IBD vs. non-IBD patients in King Abdulaziz Medical City (KAMC).

This retrospective descriptive study was carried out between 2016 and 2020. Data of 89 patients reported with CDI in KAMC were analyzed for demographics and correlations between various characteristics such as BMI, personal/family history of IBD, infection with CDI, diagnosis, method of diagnosis, and treatment modalities.

Of the total 89 CDI patients, 59 (66.3%) were adults and 30 (33.7%) were pediatric, of which 36 (40.4%) were females and 53 (59.6%) were males. PCR was the main method of choice for the diagnosis of CDI (89.9%) followed by a positive-culture result (10.0%). Seventy-eight (87.6%) CDI patients were found to be immunocompromised, with two patients diagnosed with IBDs, one with UC, and one with CD. The recurrence rate was 38.4 (30 patients) among the immunocompromised group in comparison to 27.2 (3 patients) in the immunocompetent group (p=0.584).

In this study, we found that adults were more prone to CDI infection, especially within hospital settings, and most of the CDI infections occurred in immunocompromised individuals, with cancer as the most common cause of it.

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn's disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group.

The intestinal tract harbors diverse microorganisms, host- and microbiota-derived metabolites, and potentially harmful dietary antigens. The epithelial barrier separates the mucosa, where diverse immune cells exist, from the lumen to avoid excessive immune reactions against microbes and dietary antigens. Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, is characterized by a chronic and relapsing disorder of the gastrointestinal tract. Although the precise etiology of IBD is still largely unknown, accumulating evidence suggests that IBD is multifactorial, involving host genetics and microbiota. Alterations in the metabolomic profiles and microbial community are features of IBD. Advances in mass spectrometry-based lipidomic technologies enable the identification of changes in the composition of intestinal lipid species in IBD. Because lipids have a wide range of functions, including signal transduction and cell membrane formation, the dysregulation of lipid metabolism drastically affects the physiology of the host and microorganisms. Therefore, a better understanding of the intimate interactions of intestinal lipids with host cells that are implicated in the pathogenesis of intestinal inflammation might aid in the identification of novel biomarkers and therapeutic targets for IBD. This review summarizes the current knowledge on the mechanisms by which host and microbial lipids control and maintain intestinal health and diseases.

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.

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.

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.

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.

Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD.

A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT.

Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.

Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia.

Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.

Using health administrative data and validated algorithms, we identified all children (<16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.

The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05).

Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

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.

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.

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.

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.

Risk factors and consequences associated with Clostridioides difficile infection (CDI) in children and adolescents with inflammatory bowel disease (IBD) are still uncertain. We conduct a systematic review and meta-analysis to assess risk factors and outcomes associated with CDI in children and adolescents with IBD.

PubMed, EMBASE and Cochrane Library databases were searched from inception to 24th February, 2021. Studies investigating risk factors, bowel surgery rate in pediatric IBD patients with and without CDI were included. Random-effects model was used for calculating summary estimates. Newcastle-Ottawa scale (NOS) was used for quality assessment.

Fourteen studies, comprising 17,114 patients, were included. There was a significant association between 5-aminosalicylic acid (5-ASA) use and CDI [odds ratio (OR) = 1.95, 95% confidence interval (CI) 1.26-3.03], with minimal heterogeneity (I² = 0.00%). Increased risk of active disease (OR = 4.66, 95% CI 2.16-10.07) were associated with CDI in those studies performed in high quality score (NOS > 6) and significantly higher CDI rates in studies conducted outside USA (OR = 2.94, 95% CI 1.57-5.58). The bowel surgery rate in IBD with CDI was 3.8-57.1%, compared to that in IBD without CDI (0-21.3%). All studies were of moderate to high quality.

5-ASA use and active disease might be risk factors associated with CDI in children and adolescents with IBD. Bowel surgery rates associated with CDI in IBD patients varied greatly. Large-scale clinical studies on CDI in children and adolescents with IBD are still needed to verify risk factors and outcomes.

Clostridioides difficile infection (CDI) is an important cause of inflammatory bowel disease (IBD) exacerbation and is associated with increased risk of hospitalization, colectomy, and mortality. Previous analysis have reported an increasing rate of CDI and associated mortality in IBD patients. We examined the trends in CDI-associated outcomes in hospitalized patients with Crohn's disease (CD) and ulcerative colitis (UC) over the last decade.

We used data from the National Inpatient Sample to identify patients hospitalized with both CDI and IBD from 2006 to 2014. Outcomes included in-hospital mortality, partial/total colectomy, hospital length of stay, and charges. Analysis included univariate and multivariate regression analysis.

Between 2006 and 2014, CDI-related hospitalizations increased in both CD (1.6% to 3.2%; P<0.001) and UC (4.9% to 8.6%; P<0.001). CDI-associated mortality in CD and UC patients decreased from 2.4% to 1.2% (P<0.001) and 11.3% to 9.7% (P<0.001), respectively. CDI-associated colectomy rate increased from 4.3% to 8.8% (P<0.001) in UC but decreased from 4.5% to 2.8% (P<0.001) in CD. In multivariable analysis, compared with 2006, there was a nonsignificant decrease in mortality in 2014 in both CD [adjusted odds ratio (AOR) 0.56, 95% confidence interval (CI) 0.25-1.24] and UC (AOR 0.81, 95% CI 0.61-1.07), but a significant increase in colectomy in 2014 only in UC (AOR 2.12, 95% CI 1.46-3.06).

CDI rates have increased in CD and UC over the last decade. Although there has been a significant increase in colectomies in UC, CDI-associated mortality in CD and UC has not increased over this time.

Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.

Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.

Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).

This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.

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.

To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD.

A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI.

The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05).

The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.

Trillions of microbes exist in the human body, particularly the gastrointestinal tract, coevolved with the host in a mutually beneficial relationship. The main role of the intestinal microbiome is the fermentation of non-digestible substrates and increased growth of beneficial microbes that produce key antimicrobial metabolites such as short-chain fatty acids, etc., to inhibit the growth of pathogenic microbes besides other functions. Intestinal microbiota can prevent pathogen colonization through the mechanism of colonization resistance. A wide range of resistomes are present in both beneficial and pathogenic microbes. Giving antibiotic exposure to the intestinal microbiome (both beneficial and hostile) can trigger a resistome response, affecting colonization resistance. The following review provides a mechanistic overview of the intestinal microbiome and the impacts of antibiotic therapy on pathogen colonization and diseases. Further, we also discuss the epidemiology of immunocompromised patients who are at high risk for nosocomial infections, colonization and decolonization of multi-drug resistant organisms in the intestine, and the direct and indirect mechanisms that govern colonization resistance to the pathogens.

The study's objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba.

Our longitudinal population-based cohort was comprised of all children and young adults aged <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. The Fisher exact test was used to examine the relationship between categorical variables. A Cox regression model was used to estimate the risk of CDI development in IBD patients.

Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33-15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46-13.10) and anti-tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11-9.90). The recurrence rate of CDI in our pediatric IBD population was 25%.

Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy.

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.

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.

Clostridioides difficile infection and colonization are common in pediatric Crohn's disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery.

A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery.

The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2-16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2-120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery.

A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn's disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.

Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy.

Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used.

We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome.

125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (U_Mann-Whitney=6. p=0.04).

Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy.

Evidence suggests use of proton pump inhibitors (PPIs) and H₂ blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD.

This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS.

The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H₂ blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1-11.7) for PPIs and 1.6 (95% CI, 0.7-3.7) for H₂ blockers.

Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.

BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's & Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.

Fecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children.

Nine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0.

All children had resolution of CDI. AMR genes decreased post-FMT (P < .001), with a sustained decrease in multidrug resistance genes (P < .001). Tetracycline resistance genes increased post-FMT (P < .001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P < .001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P < .001), with an increase post-FMT (P ≤ .002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P < .001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P = .008 and P = .040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT.

FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT.

The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is widely identified worldwide. This study aimed to investigate the phenotypic characterization and molecular typing of Clostridium difficile isolates among patients with UC at an inflammatory bowel disease clinic in Iran.

In this cross-sectional study, conducted from April 2015 to December 2015, 85 UC patients were assessed for C.difficile infection (CDI). C. difficile isolates were characterized based on their toxin profile and antimicrobial resistance pattern. Multi-locus sequence typing analysis (MLST) and PCR ribotyping were performed to define the genetic relationships between different lineages of toxigenic strains.

The prevalence of C. difficile isolates was 31.8% (27/85) in patients, of those 15 patients (17.6%) had CDI. Three different sequence types (STs) identified based on MLST among the toxigenic isolates, that is ST54 (33.3%), ST2 (53.3%), and ST37 (13.6%). C. difficile strains were divided into four different PCR-ribotypes (012, 014, 017 and IR1). The most common ribotype was 014 accounting for 48.3% (7/15) of all strains. The strains isolated during the first episode and recurrence of CDI usually belonged to PCR ribotype 014 (ST2). A high rate of CDI recurrence (14.1%, 12/85) experienced in UC patients. Colonization of the gastrointestinal tract with non-toxigenic C. difficile strains was frequent among patients with mild disease. All C. difficile isolates were susceptible to metronidazole, and vancomycin, 86 and 67% of isolates were resistant to clindamycin and erythromycin respectively. There was no correlation between the toxin type and antibiotic resistance (p > 0.05).

Overall CDI is rather prevalent in UC patients. All patients with CDI experienced moderate to severe disease and exposed to different antimicrobial and anti-inflammatory agents. Close monitoring and appropriate management including early detection and fast treatment of CDI will improve UC outcomes.

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.

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.

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.

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.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.