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Treatment with 20 mg of zinc daily for 10 to 14 days in children with acute diarrhea has been shown to improve diarrhea but increase vomiting. In this randomized trial involving children in Tanzania and India, 5 mg and 10 mg of daily zinc were noninferior to 20 mg of zinc for diarrhea and resulted in less vomiting.

Background Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection. Methods A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment. Results Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment ( n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events. Conclusions RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months. Clinical Trial Registration NCT03244644; 9 August, 2017. Infographic AKN5i_vZYNJMF_jRRaL_sV Video abstract: (MP4 62,291 KB) Plain Language Summary Clostridioides difficile is a diarrhea-causing bacterium that is associated with potentially serious and fatal consequences. Antibiotics used to treat or prevent infections have a side effect of damaging the healthy protective gut bacteria (microbiota). Damage to the gut microbiota can allow C. difficile to over-grow and produce toxins that injure the colon. Paradoxically, the standard of care treatment of C. difficile infection (CDI) is antibiotics. Although initially effective for the control of diarrhea, antibiotics can leave a patient at risk for CDI recurrence after antibiotic treatment is stopped. Live biotherapeutic products are microbiota-based treatments used to repair the gut microbiota. These products have been shown to reduce the recurrence of CDI. RBX2660 is an investigational microbiota-based live biotherapeutic. RBX2660 contains a diverse set of microorganisms. RBX2660 has been developed to reduce CDI recurrence in adults following antibiotic treatment for recurrent CDI. This study was conducted to demonstrate that RBX2660 is effective and safe in treating patients with recurrent CDI. Treatment was considered successful in participants who did not experience CDI recurrence within 8 weeks after administration. Overall, statistical modeling demonstrated that 70.6% of participants treated with RBX2660 and 57.5% of participants treated with placebo remained free of CDI recurrence through 8 weeks. A 13.1 percentage point increase in treatment success was observed with RBX2660 treatment compared with placebo. In participants who achieved treatment success at 8 weeks, more than 90% remained free of CDI recurrence through 6 months. The most common side effects with RBX2660 treatment were abdominal pain and diarrhea. No serious treatment-related side effects were reported. The current data from the comprehensive clinical development program support a positive benefit-risk profile for RBX2660 in the reduction of CDI recurrence in adults following antibiotic therapy for recurrent CDI.

Approximately 12% of all diarrhoeal episodes last for 7-13 days. As such, they are termed prolonged diarrhoea, and are associated with over two-thirds of all diarrhoeal deaths. Due to a lack of robust data, we aimed to evaluate a comparative background characteristics of young children with acute and prolonged diarrhoea, and their outcomes at day 90 follow-up. We performed a secondary analysis of data from the Antibiotics for Children with Diarrhea (ABCD) trial. Children aged 2-23 months were enrolled between July 2017 and July 2019 from seven Asian and sub-Saharan African countries. For this analysis, we divide diarrhoea into two categories: acute diarrhoea (duration <7 days) and prolonged diarrhoea (duration ≥7-13 days). We used logistic regression to observe baseline crude and adjusted associations and linear regression to compare post-discharge outcomes. We analysed data on 8266 children, of whom 756 (9%) had prolonged diarrhoea and 7510 (91%) had acute diarrhoea. Pakistan had the highest proportion of children with prolonged diarrhoea (n/N = 178/1132, 16%), while Tanzania had the lowest (n/N = 12/1200, 1%). From an analysis that adjusted for sex, breastfeeding, nutritional status, clinical presentation, housing, water supply, sanitation, and country, we observed that presentation at a health facility with prolonged diarrhoea was associated with low age (2-12 months) (adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.02, 1.53; P = 0.028), presence of three or more under-five children in the family (aOR = 1.54; 95% CI = 1.26, 1.87; P < 0.001), maternal illiteracy (aOR = 1.45; 95% CI = 1.21, 1.74, P < 0.001), moderate underweight (aOR = 1.25; 95% CI = 1.01, 1.55; P = 0.042) and pathogen (Campylobacter) (aOR = 1.27; 95% CI = 1.12, 1.44; P < 0.001). At day 90 follow-up, children with prolonged diarrhoea had significantly lower weight-for-age z-score compared to children with acute diarrhoea (-1.62, standard deviation (SD) = 1.11 vs -1.52, SD = 1.20; P = 0.032), as well as significantly higher frequency of hospital admission (6.1% vs 4.5%; P = 0.042). Prolonged diarrhoea was more common in children of younger age, those who were moderately underweight, those with Campylobacter in stool, those with three or more under-five children in a family, and those with illiterate mothers compared to those who had acute diarrhoea. Children with prolonged diarrhoea more often required hospitalisation during the three-month follow-up period compared to their counterparts.

Migalastat stabilizes mutant α-galactosidase in Fabry's disease, reducing globotriaosylceramide deposition. In this study, the percentage of patients with a decrease of 50% or more in kidney interstitial capillary deposition at 6 months was similar in the migalastat and placebo groups. Fabry’s disease is a rare, progressive, and devastating X-linked disorder caused by the functional deficiency of lysosomal α-galactosidase. 1 The resultant accumulation of glycosphingolipids, predominantly globotriaosylceramide (GL-3), can lead to multisystem disease and early death. 2 Binding of the pharmacologic chaperone migalastat to the active site of α-galactosidase stabilizes certain mutant enzymes, thus facilitating proper trafficking to lysosomes, where dissociation of migalastat allows α-galactosidase to catabolize accumulated substrates. 3 – 7 In patients with mutant enzymes that are identified with the validated assay, orally administered migalastat may be an alternative treatment option for addressing certain unmet medical needs associated with enzyme-replacement therapy — for . . .

Clostridium difficile infection can be life-threatening and difficult to treat, with frequent relapses. In this study in patients with recurrent C. difficile –associated diarrhea, infusion of healthy donor feces significantly decreased relapses, as compared with vancomycin therapy. Antibiotic treatment for an initial Clostridium difficile infection typically does not induce a durable response in approximately 15 to 26% of patients. 1 – 3 An effective treatment against recurrent C. difficile infection is not available. Generally, repeated and extended courses of vancomycin are prescribed. 4 The estimated efficacy of antibiotic therapy for a first recurrence is 60%, a proportion that further declines in patients with multiple recurrences. 2 , 5 – 7 Mechanisms that have been proposed for recurrence include persistence of spores of C. difficile, diminished antibody response to clostridium toxins, and persistent disturbance with a reduced diversity of intestinal microbiota. 8 – 12 Infusion of . . .

Background Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 13 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. Results MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium , Prevotella , and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). Conclusions This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. Trial registration This trial was registered on the ClinicalTrials.gov, with the registration number  NCT02504554

Background. Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI. Methods. In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available. Results. The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon. Conclusions. In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations. Clinical Trials Registration. NCT01226992.

In two randomized trials, eluxadoline was more effective than placebo in reducing abdominal pain and improving stool consistency in patients who had irritable bowel syndrome with diarrhea. Pancreatitis developed in 5 of 1666 patients (0.3%) who received eluxadoline. The irritable bowel syndrome (IBS) with diarrhea is a common functional gastrointestinal disorder that is characterized by recurring abdominal pain, bloating, and loose, frequent stools in the absence of structural, inflammatory, or biochemical abnormalities. IBS with diarrhea is associated with impairment in health-related quality of life, places a considerable financial burden on society because of reduced work productivity, and increases the use of health-related resources. 1 , 2 IBS is the most frequent diagnosis in gastroenterology practices and one of the most frequent diagnoses in primary care practices. 3 Current treatment options for IBS with diarrhea are limited. Initial therapies include dietary and . . .

In two trials involving patients with irritable bowel syndrome without constipation, 2 weeks of treatment with the minimally absorbed antibiotic rifaximin was more effective than placebo in providing adequate relief of symptoms. The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurring symptoms of abdominal pain, bloating, and altered bowel function in the absence of structural, inflammatory, or biochemical abnormalities. 1 IBS often does not respond to current treatment options, including dietary and lifestyle modifications, fiber supplementation, psychological therapy, and pharmacotherapy. 2 , 3 Because no reliable biologic or structural markers have been identified, the effects of pharmacotherapy are typically assessed by asking patients to report whether they had adequate relief of IBS symptoms (with a binary response of yes or no). 4 Given the limitations of available therapies, there is an unmet . . .

Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA. In this multicentre, double-blind, randomised, non-inferiority trial, we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009. Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection. Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment. An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient. Participants and investigators were masked to treatment allocation. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat and per-protocol populations were analysed. This study is registered with ClinicalTrials.gov, number NCT00468728. Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin. After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population. 198 (91·7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90·6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97·5% CI −4·3%). Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87·7%) of 252 patients given fidaxomicin and 223 (86·8%) of 257 given vancomycin cured (one-sided 97·5% CI −4·9%). In most subgroup analyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90·2%] of 51) than with vancomycin (33 [73·3%] of 45; p=0·031). Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7·6%) of 264 patients given at least one dose of fidaxomicin and 17 (6·5%) of 260 given vancomycin died. Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin. Optimer Pharmaceuticals.