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BACKGROUND: Increasing the influenza vaccination rate in health care workers (HCWs) promotes patient safety as well as employee health. The average HCW influenza vaccination rate is approximately 35%. Various studies have analyzed the reasons for the low vaccination rate in HCWs and developed strategies aimed at increasing this rate. METHODS: At the study hospital, the Nursing Department was contacted to recruit influenza (flu) coordinators from the various hospital departments to coordinate administration of influenza vaccinations in their respective departments, with the aim of increasing HCW vaccination rates. The flu coordinators received education about the influenza vaccine along with lists of employees, vaccination supplies, and consent/declination forms. Each flu coordinator was responsible for contacting the employees in his or her department/unit. Both consent and declination responses were documented. RESULTS: Of the hospital's 3238 employees (including physicians), a total of 2534 were contacted (78%). Of these, 2008 consented to receive the influenza vaccine and 526 declined. This represented a 37% increase in the total number of HCWs contacted and a 20% increase in vaccine recipients over the previous influenza season. CONCLUSIONS: Partnering with the Nursing Department increased the accessibility to and acceptance of influenza vaccination among HCWs. The HCWs reported positive experiences about receiving the vaccine in the work environment. [ABSTRACT FROM AUTHOR]

Intestinal tuft cells are rare cells that regulate diverse functions. They harbor chemosensory receptors and signal to the mucosal immune system in response to external stimuli, though their full function and structure remain unclear. Named for their apical "tuft" of long actin-rich microvilli, tuft cells facilitate chemoreception and other physiological responses. In enterocytes, microvilli are stabilized by intermicrovillar adhesion complexes (IMACs) composed of several proteins, including cadherin-related family member-2 (CDHR2) and cadherin-related family member-5 (CDHR5), Myosin 7b, and Usher syndrome type 1 C (USH1C). We hypothesized that IMACs would be enriched in tuft cells to regulate microvillar organization. Immunostaining of murine intestinal tissue revealed that CDHR2 and CDHR5 colocalize with the tuft cell markers, DCLK1, phospho-EGFR, advillin, and cytokeratin 18. CDHR2 was dispersed throughout murine tuft cells, while CDHR5 was concentrated on the apical surface. USH1C and Myosin 7b were present in tuft cells, but at lower levels. Human single-cell RNA sequencing revealed robust CDHR2 and CDHR5 expression in tuft cells in the small intestine and colon. Immunostaining of human intestinal tissue confirmed CDHR2 and CDHR5 localization to the apical surface of tuft cells. Our findings demonstrate that protocadherins are key components of murine and human intestinal tuft cells., Competing Interests: Competing InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients., Methods: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored by Combined Annotation Dependent Depletion for deleteriousness. Gene networks carrying susceptibility SNVs were created. Myosin 5b immunofluorescence was also studied., Results: Fifty-six patients met inclusion criteria, and 32.1% identified as Hispanic. Monogenic disease was infrequent (8.9%). Significant enrichment of GOI susceptibility SNVs was observed, notably in MYO5B, especially in Hispanics. MEFV, TNFAIP3, SH3TC2, and NCF2 were also central participants in the GOI networks. Myosin 5b immunofluorescence in colonic mucosa was significantly reduced in those with MYO5B susceptibility SNVs compared with control subjects. Seven genes (ESRRA, HLA-DQ1, RETSAT, PABPC1, PARP4, CCDC102A, and SUSD2) were central participants in the non-GOI networks., Conclusions: Our results support the polygenic nature of VEO-IBD, in which key participants, like MYO5B, were identified through network analytics. Rare variant load within susceptibility genes may be relevant not only for the genetic origins of inflammatory bowel disease, but also for the age of disease onset. Our findings could guide future work in precision medicine., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: When it comes to readiness to transition to an adult subspecialty clinic, perspectives between patients with inflammatory bowel disease (IBD) and their caregivers may differ and influence the ability to successfully transition. Patients with IBD have been shown to suffer from poor transfers of care. There is a need to more efficiently and accurately assess transition readiness to improve the transfer process., Methods: Patients transferring to an adult subspecialty clinic and their caregivers were each administered the Transition Readiness Assessment Questionnaire and IBD Self-Efficacy Scale-Adolescent. Differences between patient and caregiver responses and agreement among each dyad were tested., Results: There were 29 dyads of patients and caregivers who enrolled. There was no difference between patient and caregiver total scores. The average level of agreement between patients and caregivers was 78%. There was no association between patient response and their age, gender, ethnicity, age at time of transfer, age at diagnosis, or number of emergency room visits in the prior year., Conclusions: Patient-reported readiness to transition to adult care was confirmed by their caregivers using validated readiness assessment tools. As transition clinics must focus on high-yield interventions, a readiness survey of young adult patients without a survey of their caregivers may be adequate. However, as experts in each patient's journey, caregivers may be utilized when setting goals and priorities for a transition readiness program. The surveys used in this study can be used broadly to aid subspecialty clinics that are trying to improve the transition process., Competing Interests: Sarah N. Horst, MD, MPH- consultant and advisory board for Abbvie, Jannsen, USB, Takeda, and Gilead; Robin L. Dalal, MD- Consultant and advisory board for Abbvie; Baldeep Pabla, MD- Advisory board for BMS and Jannsen, Consultant for Abbvie and Ossium Health; David A. Schwartz, MD- consultant for Abbvie, Genetech, Gilead, Janssen, Pfizer, Takeda, and UCB. Dawn Beaulieu- consultant and the advisory board for Abbvie, Takeda, consultant for Bristol Myers Squibb, Celltrion, and the Institute of Functional Medicine. For the remaining authors, none is declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF., Methods: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed., Results: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone., Conclusion: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest relevant to this work., (Copyright © 2023 European Cystic Fibrosis Society. All rights reserved.)

The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores the function of the pathogenic mutated CF transmembrane conductance regulator (CFTR) channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in body mass index and percent predicted forced expiratory volume in one second, and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus , the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.IMPORTANCECystic fibrosis (CF) is an autosomal recessive disease with significant gastrointestinal symptoms in addition to pulmonary complications. Recently approved treatments for CF, CF transmembrane conductance regulator (CFTR) modulators, are anticipated to substantially improve the care of people with CF and extend their lifespans. Prior work has shown that the intestinal microbiome correlates with health outcomes in CF, particularly in children. Here, we study the intestinal microbiome of children with CF before and after the CFTR modulator, ELX/TEZ/IVA. We identify promising improvements in microbiome diversity, reduced measures of intestinal inflammation, and reduced antibiotic resistance genes. We present specific bacterial taxa and protein groups which change following ELX/TEZ/IVA. These results will inform future mechanistic studies to understand the microbial improvements associated with CFTR modulator treatment. This study demonstrates how the microbiome can change in response to a targeted medication that corrects a genetic disease., Competing Interests: The authors declare no conflict of interest.

Iron is indispensable for almost all forms of life but toxic at elevated levels 1-4 . To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis 1,5,6 . Recent studies showed that three Gram-negative environmental anaerobes produce iron-containing ferrosome granules 7,8 . However, it remains unclear whether ferrosomes are generated exclusively by Gram-negative bacteria. The Gram-positive bacterium Clostridioides difficile is the leading cause of nosocomial and antibiotic-associated infections in the USA 9 . Here we report that C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. We found that a membrane protein (FezA) and a P 1B6 -ATPase transporter (FezB), repressed by both iron and the ferric uptake regulator Fur, are required for ferrosome formation and play an important role in iron homeostasis during transition from iron deficiency to excess. Additionally, ferrosomes are often localized adjacent to cellular membranes as shown by cryo-electron tomography. Furthermore, using two mouse models of C. difficile infection, we demonstrated that the ferrosome system is activated in the inflamed gut to combat calprotectin-mediated iron sequestration and is important for bacterial colonization and survival during C. difficile infection., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

Patients with CF (pwCF) have high antibiotic use and an altered intestinal microbiome, known risk factors for infection with Clostridioides difficile. However, in adults with CF, C. difficile infection (CDI) is uncommon and asymptomatic colonization with C. difficile occurs frequently, for reasons that remain unclear. We investigated the rate, risk factors, and sequelae of asymptomatic C. difficile colonization in children with CF (cwCF). We identified that 32% of cwCF were colonized with C. difficile without acute gastrointestinal symptoms. Higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) were significantly associated with C. difficile colonization. No children developed symptomatic CDI in 90-days following enrollment., Competing Interests: Conflicts of Interest All authors declare that they have no conflicts of interest relevant to this work., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Alpha-gal syndrome is an immunoglobulin E (IgE)-mediated delayed hypersensitivity reaction to nonprimate mammalian products, which has a newly established gastrointestinal (GI) phenotype in adults. We assessed the GI presentation and treatment response in children., Methods: This is a retrospective study of patients presenting in a pediatric gastroenterology clinic tested for alpha-gal IgE., Results: Forty of 199 patients (20%) tested had a positive alpha-gal-specific IgE, with 77.5% reporting GI symptoms in isolation. Of the 30 that attempted dietary elimination, 8 (27%) experienced full resolution of symptoms., Discussion: Alpha-gal syndrome can present with isolated GI symptoms in children., (Copyright © 2023 by The American College of Gastroenterology.)

D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT)., Objectives: To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention., Search Methods: We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022., Selection Criteria: We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD., Data Collection and Analysis: Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence., Main Results: We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD., Authors' Conclusions: FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials., Objectives: To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022., Selection Criteria: We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome., Main Results: We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I 2 = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I 2 = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates., Authors' Conclusions: In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients., Methods: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition., Results: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered., Conclusions: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Fecal microbiota transplantation (FMT) is a rapidly growing therapy aimed at reconstituting the dysbiotic microbiota of a patient with the beneficial stool microbiota of a healthy individual. The efficacy rates of FMT are very robust for recurrent Clostridioides difficile infection in both children and adults. Although complications of FMT have been reported, it is generally believed to be a safe procedure. Novel indications for FMT are being studied, with the hope that ultimately it may be useful for a variety of disorders. As this field continues to grow, however, it is necessary to consider efficacy, safety, and innovation across the lifespan. There are unique concerns regarding FMT as it pertains to children, adults, and the elderly. In this review, we seek to update clinicians, researchers, and regulators on how these factors must be balanced across the lifespan as we move forward with this innovative therapy., (Copyright © 2023 by The American College of Gastroenterology.)

Objectives: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019., Study Design: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment., Results: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P < .001). C difficile-specific testing also decreased during the study period (P < .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P < .01) and oral vancomycin use increased (P < .001)., Conclusions: Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract 1 . This microbial community has been shown to be important during infection, but there are few examples illustrating how microbial interactions can influence the virulence of invading pathogens 2 . Here we show that expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut-the enterococci-enhances the fitness and pathogenesis of Clostridioides difficile. Through a parallel process of nutrient restriction and cross-feeding, enterococci shape the metabolic environment in the gut and reprogramme C. difficile metabolism. Enterococci provide fermentable amino acids, including leucine and ornithine, which increase C. difficile fitness in the antibiotic-perturbed gut. Parallel depletion of arginine by enterococci through arginine catabolism provides a metabolic cue for C. difficile that facilitates increased virulence. We find evidence of microbial interaction between these two pathogenic organisms in multiple mouse models of infection and patients infected with C. difficile. These findings provide mechanistic insights into the role of pathogenic microbiota in the susceptibility to and the severity of C. difficile infection., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Clostridioides difficile infection (CDI) rates and outcomes can vary based on differences in testing strategy. Our aim was to assess the prevalence of toxin detection in inflammatory bowel disease (IBD) when compared to those without IBD. Secondly, the clinical outcomes of CDI in IBD were assessed using two-step testing strategies., Methods: We included patients undergoing CDI testing from four academic centers in the United States between January 1, 2018 and June 30, 2020. First the prevalence of toxin detection was compared between individuals with IBD and those without IBD. Secondly, among patients with IBD a primary composite outcome of abdominal colectomy, admission to an intensive care unit (ICU) or death within 30 days of C. difficile testing was assessed across the three categorical groups (screen positive/toxin positive, screen positive/toxin negative and screen negative assay) resulting from the two-step testing strategy., Results: When comparing individuals with a positive screening assay, patients with IBD were less likely to have toxin detected by enzyme immunoassay (EIA) as compared to the non-IBD population (22/145 (15.2%) vs. 413/1144 (36.1%), p < 0.0001). Among all patients with IBD (n = 300), twenty-five (8.3%) had a screen positive assay/toxin positive assay, 136 (45.3%) had a screen positive/toxin negative assay and 139 (46.3%) had a negative screening assay. No significant difference in the primary composite outcome was detected across the three groups (p = 0.566)., Conclusion: When compared to those without IBD, patients with IBD have a reduced proportion of cases of C. difficile with toxin positivity. Differences in clinical outcomes among patients with IBD were not detected and limited by the infrequent detection of expressed toxin., (© 2022. The Author(s).)

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.)

Competing Interests: The authors report no conflicts of interest.

With the rising rates of Clostridioides (Clostridium) difficile infection (CDI) in children, recognizing the limitations of CDI-directed antibiotic therapy, especially in recurrent CDI (rCDI), is important. Fecal microbiota transplantation (FMT), which directly targets the underlying gut dysbiosis present in rCDI, is an important treatment option to consider in rCDI. This article will summarize indications, procedures, effectiveness, and the safety of FMT for rCDI in pediatric patients. [ Pediatr Ann. 2021;50(12):e515-e521.] .

Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and has high rates of recurrent disease. As a disease associated with intestinal dysbiosis, gastrointestinal microbiome manipulation and fecal microbiota transplantation (FMT) have evolved as effective, although relatively unregulated therapeutics and not without safety concerns. FMT for the treatment of CDI has been well studied in adults with increasing data reported in children. In this review, we discuss the current body of literature on the use of FMT in children including effectiveness, safety, risk factors for a failed FMT, and the role of FMT in children with comorbidities. We also review emerging microbial therapeutics for the treatment of rCDI., (© 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.)

Abstract: Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown., Methods: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted., Results: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted., Discussion: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children., (Copyright © 2021 by The American College of Gastroenterology.)

Objectives: Recent Infectious Disease Society of America guidelines recommend multistep testing algorithms to diagnose Clostridioides difficile infection (CDI), including a combination of nucleic acid amplification-based testing (NAAT) and toxin enzyme immunoassay (EIA). The use of these algorithms in children, including the ability to differentiate between C. difficile colonization and CDI, however, has not been evaluated., Methods: We prospectively enrolled asymptomatic pediatric patients with cancer, cystic fibrosis (CF), or inflammatory bowel disease (IBD) and obtained a stool sample for NAAT testing. If positive by NAAT (colonized), EIA was performed. In addition, children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were enrolled, and EIA was performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was also applied to stool samples from both the colonized and symptomatic cohorts., Results: Of the 225 asymptomatic children enrolled in the study, 47 (21%) were colonized with C. difficile including 9/59 (15.5%) with cancer, 30/92 (32.6%) with CF, and 8/74 (10.8%) with IBD. An additional 41 children with symptomatic CDI were enrolled. When symptomatic and colonized children were compared, neither EIA positivity (44% vs 26%, P = 0.07) nor CCNA positivity (49% vs 45%, P = 0.70) differed significantly or were able to predict disease severity in the symptomatic cohort., Conclusions: Use of a multistep testing algorithm with NAAT followed by EIA failed to differentiate symptomatic CDI from asymptomatic colonization in our pediatric cohort. As multistep algorithms are moved into clinical care, the pediatric provider will need to be aware of their limitations., 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.)

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background & Aims: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI., Methods: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT., Results: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations., Conclusions: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT., (© The Author(s) 2019. 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.)

Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

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.

Background: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD., Objectives: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD., Search Methods: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index., Selection Criteria: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention., Data Collection and Analysis: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria., Main Results: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence)., Authors' Conclusions: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.

BACKGROUND Infants and young children are frequently colonized with C. difficile but rarely have symptomatic disease. However, C. difficile testing remains prevalent in this age group. OBJECTIVE To design a computerized provider order entry (CPOE) alert to decrease testing for C. difficile in young children and infants. DESIGN An interventional age-targeted before-after trial with comparison group SETTING Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, Tennessee. PATIENTS All children seen in the inpatient or emergency room settings from July 2012 through July 2013 (pre-CPOE alert) and September 2013 through September 2014 (post-CPOE alert) INTERVENTION In August of 2013, we implemented a CPOE alert advising against testing in infants and young children based on the American Academy of Pediatrics recommendations with an optional override. We further offered healthcare providers educational seminars regarding recommended C. difficile testing. RESULTS The average monthly testing rate significantly decreased after the CPOE alert for children 0-11 months old (11.5 pre-alert vs 0 post-alert per 10,000 patient days; P<.001) and 12-35 months old (61.6 pre-alert vs 30.1 post-alert per 10,000 patients days; P<.001), but not for those children ≥36 months old (50.9 pre-alert vs 46.4 post-alert per 10,000 patient days; P=.3) who were not targeted with a CPOE alert. There were no complications in those children who testing positive for C. difficile. CONCLUSIONS The average monthly testing rate for C. difficile for children <35 months old decreased without complication after the use of a CPOE alert in those who tested positive for C. difficile. Infect Control Hosp Epidemiol 2017;38:542-546.

Background: The management of Clostridium difficile infection (CDI) in children is complicated by recurrence rates of 20%-30%. The identification of risk factors associated with recurrent disease might allow early recognition of those children at highest risk., Methods: Pediatric patients with CDI were identified through clinical laboratory records at 2 tertiary-care children's hospitals from March 2013 through May 2014. Subjects were enrolled and followed for 60 days to assess for recurrent CDI (rCDI). Blood samples were obtained at enrollment to evaluate host interleukin (IL)-8 polymorphisms and anti-toxin A antibody levels; stool samples were obtained for inflammatory markers (lactoferrin, calprotectin, IL-8) and C. difficile ribotype 027 strain status. Thirty days post enrollment, another serum sample was obtained to compare antibody responses., Results: Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. At enrollment, children with malignancy had significantly lower stool calprotectin, lactoferrin and IL-8 than those without malignancy. There was a trend toward increased stool inflammatory markers in those who later developed rCDI. The IL-8 A/A genotype was not associated with recurrent disease. No patients were found to have ribotype 027 or an antibody increase to toxin A., Conclusions: The rate of rCDI in our pediatric cohort was 30%. Children with rCDI had a trend toward higher fecal inflammatory markers with the initial infection, and these values were lower in children with malignancy. Fecal lactoferrin, calprotectin and IL-8 should be further studied to determine their value in predicting the risk of rCDI in children.

Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile., Competing Interests: The authors declare no competing financial interest.

Objective: To detect the etiologic agents of acute gastroenteritis (AGE) in children using broad molecular-based techniques, and compare clinical presentations among etiologies., Study Design: This was a prospective population-based surveillance study of children aged <6 years with AGE conducted between 2008 and 2011 as part of the New Vaccine Surveillance Network. Stools from patients and healthy controls were tested for 21 gastrointestinal pathogens using the analyte-specific reagent Gastrointestinal Pathogen Panel and an additional reverse transcription real-time polymerase chain reaction assay for sapovirus and astrovirus., Results: Of the 216 stool samples from patients with AGE, 152 (70.4%) tested positive for a pathogen, with norovirus genogroup II (n = 78; 36.1%) and Clostridium difficile (n = 35; 16.2%) the most common pathogens detected. Forty-nine patients (22.7%) tested positive for more than 1 pathogen, including 25 (71%) with a C difficile detection. There were no significant clinical differences among the patients with no pathogen detected, those with a single pathogen detected, and those with ≥2 pathogens detected., Conclusion: Using a broad molecular testing approach, high rates of enteropathogens were detected in children with AGE, dominated by norovirus genogroup II and C difficile. Coinfections were common but had no identifiable impact on clinical manifestations. As routine diagnostics of AGE progressively evolve toward nucleic acid-based pathogen detection, ongoing systematic studies are needed to better analyze the clinical significance of results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although cutaneous manifestations are the most common extraintestinal manifestation of inflammatory bowel disease, metastatic Crohn's disease (MCD) is rare. MCD is defined as the presence of noncaseating granulomatous inflammation and perivascular infiltrate in the cutaneous tissue that is noncontiguous to the gastrointestinal tract. MCD rarely involves the genitourinary tract in children. When it does, it can present as external genitalia swelling, erythema, plaques, or ulcerations. Here we present three pediatric cases of MCD involving the genitourinary tract. In addition to discussion of the presented cases, we have reviewed the literature on the genitourinary presentation of MCD in the pediatric population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

CDIs are on the rise in both hospital and community settings in adults and children. Children with cancer or a history of HSCT or SOT appear to be at higher risk for primary disease, recurrent disease, and severe outcomes when compared to children with other comorbidities. The reasons for this are not clear and no studies to date have analyzed risk factors for CDI in pediatric transplant patients. Colonization rates in children with cancer and a transplant history are also high. Determining which children are colonized with Clostridium difficile and symptomatic from another source vs. symptomatic from CDI is difficult and a clinical conundrum for the transplant physician. The use of fecal transplantation for severe or rCDI is likely safe and effective in the immunosuppressed pediatric cancer or transplant patient, but this will need to be more thoroughly studied in this patient population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Clostridium difficile, a common cause of antibiotic-associated diarrhea, has been reported to recur in high rates in adults. The rates and risk factors for recurrent C difficile infection (rCDI) in children have not been well established., Methods: We conducted a retrospective cohort study of 186 pediatric patients seen at a tertiary care referral center for a 5-year period diagnosed as having a primary C difficile infection. Children with recurrent disease, defined as return of symptoms of C difficile infection and positive testing ≤60 days after the completion of therapy, were compared with children who did not experience an episode of recurrence., Results: Of the 186 pediatric patients included in this study, 41 (22%) experienced rCDI. On univariable analysis, factors significantly associated with rCDI included malignancy, recent hospitalization, recent surgery, antibiotic use, number of antibiotic exposures by class, acid blocker use, immunosuppressant use, and hospital-acquired disease. On multivariable analysis, malignancy (odds ratio [OR] 3.39, 95% confidence interval [CI] 1.52-7.85), recent surgery (OR 2.40, 95% CI 1.05-5.52), and the number of antibiotic exposures by class (OR 1.33, 95% CI 1.01-1.75) were significantly associated with recurrent disease in children., Conclusions: The rate of rCDI in children was 22%. Recurrence was significantly associated with the risk factors of malignancy, recent surgery, and the number of antibiotic exposures by class.

Duodenal stenosis and duodenal atresia are well-known gastrointestinal anomalies in patients with Down syndrome. Although duodenal atresia presents early and classically with vomiting in the immediate neonatal period, the presentation of duodenal stenosis can be significantly more subtle and the diagnosis delayed. Here, we describe the case of a 5-month-old male infant with Down syndrome and delayed presentation of high-grade duodenal stenosis diagnosed endoscopically. Pediatric gastroenterologists should include duodenal stenosis in the differential diagnosis of older infants and children with vomiting and should be familiar with the endoscopic appearance of this lesion.

Clostridium difficile is a frequent cause of antibiotic-associated diarrhea in adults and older children. However, as many as 80% of infants can be asymptomatically colonized. The reasons for this have not been well established but are believed to be due to differences in toxin receptors or toxin internalization. Determining which children who test positive for C. difficile warrant treatment is exceedingly difficult, especially in the setting of increased rates of detection and the rising risk of disease in children lacking classic risk factors for C. difficile.

Background: Staphylococcus aureus (S aureus) is the major cause of surgical site infections (SSI). At The Christ Hospital, Cincinnati, OH, S aureus accounted for over 80% of sternal wound infections in cardiac surgery patients. Approximately 700 cardiac surgeries are performed each year, with an associated infection rate of 1.8% per 100 procedures performed. In an attempt to reduce S aureus sternal wound infections, the use of prophylactic intranasal mupirocin was examined., Methods: Each patient undergoing cardiac surgery was nasally cultured before entering the operating room, and then intranasal mupirocin was applied and continued every 12 hours. Culture results were finalized within 48 hours. Mupirocin was discontinued when the culture returned negative and continued for 7 days when the culture returned positive for S aureus., Results: Cultures showed a S aureus carrier rate of 21%. These patients received mupirocin for 7 days. A decrease in S aureus-associated SSI rates was observed from a case rate of 1.68% to 0.37% per 100 procedures over a 17-month period., Conclusion: Identifying and treating S aureus carriers with a full course of mupirocin does impact the rate of S aureus surgical site infections.

Methysergide is a serotonin antagonist and is used as a long-term prophylactic treatment for migraine. Although many patients experience adequate control of migraine episodes, methysergide has been reported to cause retroperitoneal and pleuropulmonary fibrosis. Cardiovascular side effects mainly in the form of valvular fibrosis have been less recognized. We report 2 cases of methysergide-related mitral valve fibrosis.