Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

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.

Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. METHODS: Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. RESULTS: A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2-16) relapses prior to study enrollment, with 5 (range, 3-15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5-10) the day prior to FMT to 2 (IQR, 1-2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2-6) before transplant to 8 (IQR, 5-9) after transplant. No serious or unexpected adverse events occurred. CONCLUSIONS: In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. CLINICAL TRIALS REGISTRATION: NCT01704937.

Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease.

Ten children at our institution received single-infusion fecal microbiome transplant (FMT) using healthy, related screened donor stool to treat recurrent Clostridium difficile infection (RCDI) via nasogastric tube (2 patients) or colonoscopic delivery. Nine of the 10 (90%) children had resolution of their symptoms after a single-infusion FMT with follow-up of 1 month to 4 years. No concerning related adverse events were recognized during short- or long-term follow-up. Three of these children had concomitant inflammatory bowel disease and 2 of these 3 (66%) patients cleared RCDI with no clinical change in their underlying inflammatory bowel disease clinical activity as assessed by Physician's Global Assessment. All of the patients who had clinical improvement of gastrointestinal symptoms of RCDI while treated with antibiotics had lasting return of baseline health after FMT.

Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.

IMPORTANCE: Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use. OBJECTIVE: To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled. INTERVENTIONS: Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months. MAIN OUTCOMES AND MEASURES: The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements. RESULTS: No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02). CONCLUSIONS AND RELEVANCE: This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01914731.

Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis.

OBJECTIVES: We evaluated the response to infliximab in pediatric patients with ulcerative colitis (UC) and their long-term follow-up. We expanded our previous study of 14 patients and furthermore evaluated the success of weaning patients from infliximab. PATIENTS AND METHODS: We reviewed the charts of 27 pediatric patients with UC who were treated with infliximab instead of undergoing a colectomy. Patients with new-onset UC refractory to intravenous steroids for 5 to 10 days and patients with non-steroid-dependent UC with an acute exacerbation were classified as acutely ill (n = 16); patients with chronic steroid-dependent UC were classified as chronically ill (n = 11). The Lichtiger Colitis Activity Index (LCAI) was measured for all patients at baseline and at 1 and 2 months after treatment with infliximab was initiated. Patients were regarded as successfully treated if they remained off steroids and avoided colectomy. RESULTS: The acutely ill group had a mean LCAI score of 11.4 at induction and 0.3 after 2 months. The chronically ill group had a mean LCAI score of 11.2 at induction and 5.5 after 2 months. Treatment with infliximab was successful in 75% of acutely ill patients and in 27% of chronically ill patients. Infliximab was discontinued in 80% of successfully treated patients (83% of acutely ill, 67% of chronically ill). These patients had an average of 10 infusions and a mean follow-up time of 10 months from their last infliximab infusion. CONCLUSIONS: Our results suggest that infliximab is more effective in acutely ill UC patients than in patients with chronic steroid-dependent UC. In addition, some patients treated with infliximab can be weaned from infliximab and maintain remission.

Shortcomings of the inflammatory bowel disease Serology 7 panel.

OBJECTIVE: The goal was to compare the predictive values of the Prometheus Inflammatory Bowel Disease (IBD) Serology 7 (IBD7) panel (Prometheus Laboratories, San Diego, CA) with the predictive values of routine blood tests in a population of children referred for initial evaluation of suspected IBD. METHODS: Medical records of pediatric patients referred for evaluation of IBD for whom IBD7 testing was performed at Prometheus Laboratories between January 2006 and November 2008 were reviewed. Patients underwent diagnosis by pediatric gastroenterologists on the basis of clinical, radiologic, endoscopic, and pathologic evaluations. RESULTS: A total of 394 records were identified. We excluded 90 records on the basis of age of >21 years, previous diagnosis of IBD, or unclear diagnosis. The prevalence of IBD in this cohort was 38%. The sensitivity, specificity, positive predictive value, negative predictive value, and kappa value for the serological panel were 67%, 76%, 63%, 79%, and 42%, respectively, compared with values for a combination of 3 abnormal routine laboratory test results of 72%, 94%, 85%, 79%, and 47%. The antiflagellin antibody assay, the newest assay added to the panel, had sensitivity of 50% and specificity of 53%. Repeat serological testing failed to produce consistent results for 4 of 10 patients. CONCLUSION: Despite its recent inclusion of the antiflagellin assay, the IBD7 panel has lower predictive values than routine laboratory tests in pediatric screening for IBD.

Infliximab is effective in acute but not chronic childhood ulcerative colitis.

PURPOSE: The authors report their experience with infliximab in pediatric patients with ulcerative colitis (UC). METHODS: Fourteen patients were reviewed. Group 1 included five patients with newly diagnosed, fulminant colitis refractory to 7 to 10 days of intravenous steroids. Group 2 included four patients with ulcerative colitis in remission off steroid therapy who experienced relapse and were hospitalized with fulminant colitis refractory to intravenous steroids for 7 to 10 days. Group 3 included five patients chronically dependent on steroids with colitis refractory to medical management. All patients were treated on an open-label basis with infliximab infusions of 5 mg/kg/dose at 0, 2, and 6 weeks and every 6 to 8 weeks thereafter. Follow-up was maintained for at least 6 weeks. Clinical status was scored with the Lichtiger Colitis Activity Index (LCAI) at each visit. LCAI >or=10 was considered treatment failure. We defined success as LCAI or=11 before infliximab treatment. All group 1 patients experienced response to infliximab. All but one (75%) patient in group 2 had a response. Only one (20%) group 3 patient had a response to infliximab. CONCLUSION: Infliximab was an effective agent in the treatment of acute UC in our patients. Long-term steroid use and emergency colectomy were avoided. Infliximab was less effective in patients who were dependent on steroids.