GI Infections Research Articles

Biomarkers in a phase 1b study of investigational microbiome therapeutic SER-155 in adults undergoing allogeneic hematopoietic cell transplantation (allo-HCT).

6554 Background: Acute graft- versus-host disease (aGvHD) is a life-threatening complication following allo-HCT. Microbiome dysfunction and associated GI barrier disruption may contribute to aGvHD via activation of inflammatory immune responses. Circulating biomarkers in the peri-transplant period are correlated with risk of severe aGvHD, including suppression of tumorigenicity 2 (ST2), regenerating islet-derived 3-alpha (Reg3a) and inflammatory cytokines (IL6, IFNϒγ & TNFα). SER-155 is an investigational cultivated oral microbiome therapeutic designed to restructure the GI microbiome, improve GI barrier integrity and reduce GI inflammation and is being assessed in a 2-part Phase 1b study in adults undergoing allo-HCT. We present preliminary safety, GvHD, PK, and exploratory biomarker data from the completed open-label Cohort 1 through Day 100 post-HCT. Methods: Adult recipients of allo-HCT were eligible. HCT conditioning and aGvHD prophylaxis were per investigator discretion. Patients received 2 courses of SER-155 (pre-HCT and post-neutrophil engraftment, each comprised of 4 days of microbiome conditioning with oral vancomycin followed by 10 days oral SER-155. The primary endpoint was safety. Strain engraftment (PK) and biomarkers were assessed in stool and plasma samples. Results: Fifteen adults enrolled; 13 received at least 1 course of study drug (median age 67; 54% male), and 11 underwent allo-HCT. Following each course, the majority of the 16 SER-155 strains were detected in stool. Treatment-emergent adverse events (AEs) were reported in all patients with GI AEs the most common. No serious AEs (SAEs) were deemed related to SER-155. Most SAEs and AEs of special interest (ie, BSIs, invasive or GI infections) occurred between HCT and the 2nd SER-155 course. There were no deaths before Day 100. No BSIs were attributable to SER-155 strains. The rate of grade 2-4 aGvHD based on MAGIC criteria through Day 100 was 45.5%; no severe grade 3-4 aGvHD was observed. Median levels of plasma biomarkers REG3α, ST2 and inflammatory cytokines were not elevated relative to a reference range (Table). Conclusions: In this small open-label cohort, SER-155 was generally well-tolerated through Day 100 without drug-related SAEs and no severe aGvHD. Plasma biomarkers were not elevated at HCT Day 0 or neutrophil recovery. These preliminary observations align with the design and preclinical evaluation of SER-155. Clinical trial information: NCT04995653 . [Table: see text]

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

Presence of Enteric Viruses in Shellfish Samples from the Persian Gulf.

Shellfishes are a significant economic and nutritious seafood amongst people in different countries. Seafood products, particularly shellfish, are potential reservoirs of enteric viruses. This research investigated the incidence of rotavirus (RoV), norovirus (NoV) GI and GII, hepatitis A virus (HAV), and hepatitis E virus (HEV) in shellfish samples from the Persian Gulf, Iran. One hundred and fifty shellfish samples were collected. RNA extraction and cDNA synthesis were performed using commercial kits. The real-time polymerase chain reaction assessed the presence of enteric viruses in extracted cDNA samples. Thirty-two out of 150 (21.33%) shellfish samples were contaminated with enteric viruses. Prevalence rates of NoV GI, NoV GII, HAV, and RoV amongst shellfish samples were 8.00%, 11.33%, 1.33%, and 0.66%, respectively. There were no contaminated shellfish samples with HEV. Simultaneous prevalence of HAV and NoV GI, and HAV and NoV GII viruses were 0.66% and 0.66%, respectively. Examined viruses had a higher prevalence in shellfish samples collected in the winter season (P<0.05). Prevalence of HAV, RoV, NoV GI, and NoV GII amongst shellfish samples gathered in the winter season was 2.85%, 9.09%, 11.90%, and 20%, respectively. To the best of our knowledge, this was the first report of the incidence of enteric viruses, particularly HAV, NoV GI, NoV GII, and RoV, in shellfish samples from the Persian Gulf, Iran. Shellfish samples may serve as a potential source of enteric viruses for the human population. Therefore, routine viral assessments should be conducted. The consumption of fully cooked shellfish can significantly reduce the risk of HAV, RoV, NoV GI, and NoV GII infections. Furthermore, given the export value and importance of shellfish samples, their microbial quality and safety should be routinely monitored.

P232 Common variable immunodeficiency-associated enteropathy in consecutive patients from a tertiary hospital

Abstract Background Common variable immunodeficiency (CVID) patients may develop intestinal inflammatory involvement in 9-20% of cases, although its diagnosis, management and prognosis are not well established. Methods We performed a transversal study with retrospective data collection. We reviewed all clinical records from consecutive adult CVID patients followed in Gregorio Marañón Hospital (Spain) from January 1st 1990 to January 1st 2023. A diagnosis of CVID-associated enteropathy (CVID-E) was established if patchy intestinal inflammation (Crohn-like pattern) or colonic inflammation (ulcerative colitis-like pattern) was demonstrated, or villous atrophy was observed in duodenal biopsies (celiac-like pattern) or inflammatory infiltrate was observed in colonic biopsies (microscopic colitis-like pattern). Differences between CVID-E patients and the rest of the CVID cohort were evaluated using chi-square and T student methods, when appropriate. Results 89 patients with confirmed CVID following ESID criteria were included. Patients’ characteristics are summarised in Table 1. All patients were receiving intravenous or subcutaneous Igs and reached an Ig G trough level &amp;gt;1000 mg/dL. CVID-E was diagnosed in 26 patients (29,2%), at a median of 6,4 years after CVID diagnosis. Surprisingly, 10 patients (38,5%) were diagnosed with CVID-E before or at the same time of CVID diagnosis. 5 patients were dead (19,2%), and the causes of death were gastric cancer (1 patient), liver complications (1), infectious complications (1), enteropathy (1) and unknown cause (1). 73,1% suffered from GI infections (Giardia lamblia, Campylobacter jejuni and Clostridioides difficile were the most frequent agents). The most frequent pattern of the disease was Crohn-like disease (Figure 1). Although exclusive celiac-like pattern was found in only 3 patients, 5 Crohn-like, 4 UC-like and 2 microscopic colitis-like pattern patients also presented duodenal atrophy. Unexpectedly, 46,2% of CVID-E patients suffered from concomitant liver involvement. Eight patients received corticosteroids, 2 azathioprine and 1 patient received infliximab and subsequent ustekinumab. One patient needed subtotal colectomy, another ileal resection and another patient received a terminal colostomy due to severe perianal disease. CVID-E patients presented statistically more frequent liver involvement, more GI infections, and a tendency towards more GI cancer. Conclusion CVID-E is frequent among CVID patients. These patients suffer from more GI infections, liver involvement and probably more GI cancer. Screening of levels of Igs at diagnosis of IBD and celiac disease is advisable as CVID diagnosis can occur at the same time or even after enteropathy diagnosis.

Safety and Efficacy of Bacillus coagulans SNZ 1969® Probiotic Supplementation in Reducing Infections in Malnourished Children: A Randomised, Double-blind, Placebo-controlled Study

Introduction: Malnutrition, a significant global health challenge, increases children’s susceptibility to infections due to compromised immunity and altered gut microbiota. While probiotics have shown potential in improving gut health and immune responses, their efficacy in malnourished children, particularly those using Bacillus coagulans strains, remains understudied. Aim: To investigate the safety and efficacy of Bacillus coagulans SNZ 1969® among malnourished children aged between one and five years. Materials and Methods: A randomised, double-blind, placebocontrolled study was conducted at Byramjee Jeejeebhoy Government Medical College (BJGMC) and Sassoon Hospitals in Pune, Maharashtra, India among paediatric patients in the outpatient setting, after obtaining ethics committee clearance. Malnourished (moderately underweight) children were randomly allocated to either the probiotic group (B. coagulans SNZ 1969®) or the placebo group receiving the respective treatment for a duration of three months. Total days of illness, as well as the incidence of Gastrointestinal Tract (GIT) and Respiratory Tract Infections (RTIs), were assessed. Results: Out of 82 enrolled children, 46 (24 in the probiotic group and 22 in the placebo group) completed the full three-month study. A significant reduction in the total days of illness was observed in the probiotic group (p-value=0.009). Additionally, the probiotic group exhibited a slightly lower frequency of GIT and RTI episodes compared to the placebo group (1.32 vs. 1.48, p-value=0.077). A trend towards fewer days with respiratory symptoms in the probiotic group was noted compared to the placebo group (6.12±2.19 vs. 7.56±3.65; p-value=0.0687), along with a non significant decline in the occurrence of RTIs at the 31-60 and 61-90 day periods. Similar declining trends were observed for the occurrence of GI infections and total days with GI symptoms between the two groups (0.24±0.88 vs. 0.53±1.2; p-value=0.4593). B. coagulans SNZ 1969® treatment was welltolerated, and no severe adverse events were reported. Conclusion: The study demonstrated a significant reduction in the total days of illness with B. coagulans SNZ 1969® treatment compared to placebo. Additionally, B. coagulans SNZ 1969® treatment was found to be associated with a non significant decrease in the occurrence of GI and RTIs, as well as a relatively shorter duration of infection among malnourished children under five years of age.

A Study on the Effectiveness of Emperical Therapy of Antibiotics in Infective Diabetic Patient

ABSTRACT: Background: Diabetes mellitus is a known risk factor for certain infectious diseases such as skin, mucus membrane, soft tissue, urinary tract, respiratory tract and surgical or hospital associated infections. In elderly patients initial antibiotic therapy for diabetic infection is empirical. To study the efficacy of empirical antibiotic therapy is significant to ensure the potency of the given therapy. Objective: The study was aimed to determine the effectiveness of empirical antibiotic therapy in infective Diabetes Mellitus patients. Method: A Prospective observational study, conducted in inpatients who were admitted in General medicine and surgery Department. The effectiveness of antibiotics was evaluated by parameters like the length of stay, adjustment, discontinued, modified, antibiotic days, antibiotic course and treatment period. Result: There is no significant differences between sex and occurrence of infections showed sex is an independent factor for infection and age, co-morbidities, uncontrolled diabetes had the statistically significant (p&lt;0.01) association with occurrence of infections. The empirical therapy was found to be effective choice of treatment in GI tract infections patients and taking empirical therapy showed effective outcome without adjustment and modification and the 65% patients had &lt; 5 days of length of stay who were treated for diabetic foot ulcer followed by GI infections, UTIs and RTIs. Conclusion: The efficacy of the empirical antibiotic therapy was more effective in patients with GI infections as per modified and discontinuation and as per the &lt; 5 days of length of hospital stay empirical antibiotics are effective in patients with Diabetic foot infections.

Estimation of Norovirus infections in Japan: An application of wastewater-based epidemiology for enteric disease assessment

Noroviruses of genogroup I (NoV GI) and NoV GII are the primary causes of acute gastroenteritis (AGE) in developed countries. However, asymptomatic and untested NoV infections lead to an underestimation of AGE cases, and the lack of mandatory viral identification in clinical cases hinders precise estimation of NoV infections. Back estimation of NoV infections in the community using a wastewater-based epidemiology (WBE) approach can provide valuable insights into the disease's extent, progression, and epidemiology, aiding in developing effective control strategies. This study employed a one-step reverse transcription-quantitative PCR to quantify NoVs GI and GII in wastewater samples (n = 83) collected twice a week from June 2022 to March 2023 in Japan. All samples from the Winter-Spring (n = 27) tested positive for NoV GI and GII RNA, while 73 % and 88 % of samples from the Summer-Autumn (n = 56) were positive for NoV GI and NoV GII RNA, respectively. Significantly higher concentrations of NoV GI/GII RNA were found in the Winter-Spring season compared to the Summer-Autumn season. NoV RNA was consistently detected in wastewater throughout the year, demonstrating the persistence of AGE cases in the catchment, suggesting an endemic NoV infection. Estimates of NoV infection incorporated viral RNA concentrations, wastewater parameters, and signal persistence in a mass balance equation using Monte Carlo Simulation. The median estimated NoV GI infections per 100,000 population for Summer-Autumn was 133 and for the Winter-Spring season, it was 881. Estimated NoV GII infections were 1357 for Summer-Autumn and 11,997 for the Winter-Spring season per 100,000 population. The estimated NoV infections exceeded by 3.2 and 23.9 folds than the reported AGE cases in Summer-Autumn and Winter-Spring seasons, respectively. The seasonal trend of estimated NoV infections closely matched that of AGE cases, highlighting the utility of WBE in understanding the epidemiology of enteric infections.

The Importance of Endoscopy with Biopsy: Real-World Evidence of Gastrointestinal Involvement in Primary Immunodeficiency in Two Main Northern Italian Centres.

Inborn errors of immunity (IEI) represent a heterogeneous group of diseases in which the true prevalence of GI involvement is not well-known. This study evaluates the prevalence of lower GI manifestations in patients with common variable immunodeficiency (CVID), analysing the histologic findings in colonic samples and assessing any correlations with biochemical abnormalities. A retrospective study was performed by collecting the data of IEI adult patients followed up at two main Northern Italian centres. Demographic and clinical data, and blood tests were collected. A colonoscopy with multiple biopsies in standard sites, in addition to a biopsy for any macroscopic lesion, was performed. The gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) were used to assess GI symptoms. 141 patients were included: 121 (86.5%) with CVID, 17 (12.1%) with IgG subclass deficiency, and 2 (1.4%) with X-linked agammaglobulinemia. Of the patients, 72 (51%) complained of GI symptoms. No differences were seen between patients receiving or not IgRT. GI infections were found in 9 patients (6.4%). No significant correlations were found between gut infections and symptoms or leukocyte infiltrates. Colonoscopy alterations were present in 79 patients (56%), and the most common were colon polyps (42%). Microscopical abnormalities were seen in 60 histologic samples (42.5%) and the most frequent was nodular lymphoid hyperplasia (40%). A leukocyte infiltrate was present in 67 samples (47.5%), and the most common was a lymphocyte infiltrate (33%). No correlation was found between GI symptoms and macroscopic alterations, whereas a positive correlation between symptoms and microscopic alterations was detected. GI symptoms and microscopic alterations in colon samples are closely related; hence, it is important to carry out serial colonic biopsies in every CVID patient, even in the absence of macroscopic lesions.

S3421 HIV/AIDS, and MAC vs COVID Diarrhea

Introduction: During the COVID pandemic, it was difficult to differentiate COVID diarrhea vs other causes, especially in the HIV/AIDS population. HIV infected patients are at high risk for GI infections. Biopsy of the small intestine identifies etiologies which help to differentiate infection, inflammatory, and neoplastic GI disease. Case Description/Methods: A 39-year-old male presented with two months of epigastric abdominal pain, severe diarrhea, and dehydration during the COVID pandemic in 2020. Past medical history of AIDS wasting syndrome. The patient was severely hypotensive. Exam was notable for mild epigastric tenderness,and hepatomegaly. Complete blood count (CBC) revealed a Hemoglobin (Hg) of 4.3 g. COVID 19 was positive. Gastrointestinal panel PCR was negative. CD4 count 1, HIV RNA viral load 48,700. MRI of the abdomen and pelvis showed diffuse bowel wall thickening in the small intestines. On hospital day 2, Esophagogastroduodenoscopy (EGD) and Colonoscopy were performed for anemia and diarrhea, which revealed abnormal variegated mucosa in the duodenum. Colonoscopy showed a normal mucosal appearance. The pathology report of the duodenum revealed macrophages in the lamina propria, which stained positive for Acid Fast Bacilli. Duodenal biopsy showed markedly expanded lamina propria with numerous histiocytes having finely granular chromatin pattern (Panel 1 and 2). The patient was diagnosed with Mycobacterium avium-intracellulare enteritis. Discussion: This 39-year-old male presented with chronic diarrhea without fever or respiratory symptoms. The most pertinent question for the health care team was whether COVID 19 caused the diarrhea.. Endoscopy with biopsy of the small intestine was essential for an accurate diagnosis. MAC infection in HIV has been dramatically declining since the widespread use of antiretroviral therapy and prophylaxis against MAC infection compared to the 1990s (from 65.3/1000 in 1992 to 2/1000 in 2015) (1). It is important to differentiate MAC from other diseases with a macrophage infiltration or inclusions: including Whipple’s, histoplasmosis, and macroglobulinemia. Patients with MAC enteritis present with fever, and watery diarrhea with diffuse small bowel malabsorption which mimics Whipple’s disease. However, the key to differentiate these two entities is doing a duodenal biopsy showing foamy macrophages with PAS-positive acid-fast bacilli (2).Figure 1.: Histology finding.

Utilization of Probiotics in Treatment of Gastrointestinal Infections among Children

Probiotics have been extensively studied and examined globally. Probiotics are extremely important for human health and encourage the growth of good bacteria in the human body. Probiotics exert its beneficial effect in the human body through a number of mechanisms, including the production of antibacterial chemicals, the eradication of pathogenic bacteria, and the prevention of the synthesis of toxic substances. Probiotics are now available in the market as functional foods and dietary supplements. The probiotics market is expected to increase from $35.6 billion in 2015 to $64.6 billion in 2023. Lactobacillus and Bifidobacteria are the most commonly used probiotics in the infant formulas. Probiotics are extremely beneficial for the gut health. Various factors disrupt the microflora of gastrointestinal tract of infants and cause various GI infections and diseases. Methods: Previous articles have been studied to develop this review article about a broad spectrum of pediatric disorders treated with probiotics. Probiotics are helpful in the prevention of irritable bowel syndrome, constipation, diarrhoea, gastrointestinal reflux disease, inflammatory bowel disease, acute gastroenteritis, infantile colic and necrotizing enterocolitis. Different types of probiotic mixtures and probiotic bacteria are utilized in the treatment of GI diseases. Probiotics have also proved its effectiveness in the treatment of gastrointestinal conditions. Conclusion: Efforts to improve human health are concentrating on methods for modifying the indigenous microflora using live microorganisms, now referred to as “probiotics”. The probiotic market is expanding and is expected to rise to $64.6bn by the year 2023. Probiotics are now added to a variety of food products such as cereals, fruit juices and milk-based product

Parenteral vaccination strategies target protective immunity to the small and large intestine mucosa

Abstract Prophylactic vaccines are most commonly given by a parenteral route. However, this strategy often confers poor protection against GI pathogens because antigens are primarily presented in peripheral lymph nodes, which do not provide the prerequisite ‘tissue imprinting signals’ to target memory T and B cells to the gut. Here, we describe a platform that enables parenteral vaccines to target protection to the GI tract. This was achieved by subcutaneous (s.c.) delivery of compounds known to imprint gut tropism onto lymphocytes. Am80, a retinoic acid receptor agonist, targeted immunity to the small intestine through up-regulation of gut-homing receptors α4β7 and CCR9, and promotion of IgA class-switching. S.c. injection of OVA + CpG combined with repeated injections of Am80 generated significantly higher and durable fecal anti-OVA IgA titers, compared to OVA + CpG without Am80. Vaccination with Am80 also increased antigen-specific CD4 and CD8 T cell trafficking to the small intestine and generated tissue resident memory T (Trm) cells. To overcome the need for multiple doses of Am80, which can cause tissue toxicity at the injection site and hinder clinical translation, we developed a polymeric nanocarrier that showed equivalent imprinting efficacy upon a single injection, lowering the cumulative dose to one-third. Furthermore, we also developed a modified vaccination strategy that could augment effector and memory T cell responses not only in the small intestine, but also in the cecum, colon and rectum, conferring protection to the entire intestinal tract. We conclude that supplementation with mucosal imprinting signals is a promising approach to enhance parenteral vaccines by generating mucosal protection against GI infections. Supported by the Bill &amp; Melinda Gates Foundation

“A STUDY OF ETIOLOGICAL PREVALENCE OF INFECTIONS IN DIABETES MELLITUS PATIENTS IN A TERTIARY CARE HOSPITAL”

BACKGROUND: Infection is still the most common cause of morbidity and mortality in patients with Diabetes in our country. Many common infections are polymicrobial in Diabetic patients,So heightened sense of awareness about these infections will lead to early diagnosis and subsequent treatment of these potential life threatening infections,for better prognosis and also to avoid high degree of Drug resistance in them. AIM:To study the etiological agent and its responsible for the prevalence of infections in Diabetes mellitus patients. MATERIALS AND METHODS: A Hospital based observational prospective study was conducted in the department of general medicine in santhiram medical college and general hospital for 6 months,50 Diabetic patients attending patient in the department of general medicine and relevant investigations done and assessed the etiological agent responsible for prevalence of infections in diabetes mellitus patients. RESULTS: rd th Out of 50 Patients studied,the majority of the group belonged to the 3 and 4 decade which shows that Diabetes with infections are more prevalent in the middle aged people in this study. Soft tissue infections,being the commonest of the infections contributed,37% of the total patients in the study, followed by respiratory infections 30% , genitourinary infections 20% and a very small group of GI infections 7%. Nervous system infections and infections of blood infections constituted a minority of 3% and 4% respectively. CONCLUSION : rd Infections in diabetes are more in the 3 and 4 th decades. Soft tissue infections, respiratory tract infections, and genitourinary infections are more prevalent in diabetics in that order

Presentation and Patterns of Celiac Disease in Indian Subcontinent: A Literature Review

Gluten, in genetically susceptible individuals induces an immune mediated enteropathy called Celiac disease (CD). It is an established cause of malabsorption, with the worldwide prevalence being 1% in the general population. It is found across all age groups, from infants to the elderly with 20% patients being diagnosed in the seventh decade of life. It has varying clinical presentations ranging from silent asymptomatic forms which are diagnosed during screening to life threatening forms with severe malabsorption to atypical presentations, with the symptom spectrum extending beyond the gastrointestinal tract which are more common in adults. High index of suspicion, robust screening and testing, followed by strict adherence to gluten free diet is a must to curb and cure the disease. Patients tend to face difficulties not only during diagnosis, but also with compliance and availability of a gluten free diet, in addition to significant economic and psychosocial burden, which is more predominant in developing countries. Screening of high-risk groups like first-degree relatives of celiac disease, patients with severe malnutrition, other autoimmune diseases, refractory anaemia and irritable bowel syndrome should be done to enhance case detection. In low middle income countries, judicious resource utilisation takes precedence, hence, tackling a multifactorial disease such as celiac disease becomes challenging. Repeated follow ups, awareness among patients and doctors, encouragement, availability of testing and dietary counselling is necessary for management of the disease in such settings. Improving sanitation and feeding practices may also play role in decreasing incidence, considering childhood GI infections are a well-established risk factor. Increased availability of serological tests (IgA/IgG anti-tTG, anti -EMA and anti-DGP), biopsy, genetic testing and other newer modalities under research have improved the diagnostic accuracy. Poor compliance increases the risk of GI malignancy, non-Hodgkin’s lymphoma, Hepatocellular carcinoma and MALToma. Hence adherence is a must to prevent complications. A wide variety of treatment modalities are being evaluated to bring into force alternative strategies for management. Only providing gluten free diet is often not sufficient for improvement of nutritional status in patients with CD. Hence, micronutrient supplementation should also be encouraged to meet the unmet needs.

Clinico-epidemiology and assessment of folate and vitamin B12 status in severe acute malnourished children: a hospital-based observational study in the rural area of Uttar Pradesh

Background: Severe acute malnutrition (SAM) is a serious health problem in children in India. Vitamin B12 and folate are crucial micronutrients along with others required for rapid growth and development during infancy and early childhood, whereas their deficiencies contribute to malnutrition. The study aimed to evaluate iron, folate and vitamin B12 status in hospitalized SAM children aged between 6-59 months and their clinical, epidemiological profile.Methods: A hospital-based observational study on 159 children with SAM in the age group 6-59 months who were enrolled in the study based on anthropometric indicators after written informed consent from parents. The clinical, demographic profile and pertinent details of each patient were collected using standardized proforma and the blood samples were collected. Serum ferritin level was done in all anaemia cases, while vitamin B12 and folic acid (FA) were done only in children with macrocytic or dimorphic anaemia. For statistical analysis, SPSS 20.0 software was used.Results: Mean age of admitted children was 23.77±13.95 months belonging mainly to lower socioeconomic scale and joint families with preferential vegetarian diet. 39.62% SAM patients were between 6-12 months of age at the time of admission. The most common associated infections were GI infections (gastrointestinal tract) in 52.20%. Out of all cases, 93.71% of SAM patients were anaemic. 39.59% cases had macrocytic anaemia followed by microcytic anaemia in 30.20%. Of the 91 cases with macrocytic/dimorphic anaemia (based on MCV and morphology), vitamin B12 and FA levels were done, 92.30% and 61.53% had a deficiency of vitamin B12 and FA, respectively. Overall out of all admitted patients, 52.83% of SAM children had vitamin B12 deficiency and folate deficiency was found in 35.22% of children.Conclusions: SAM children had a high prevalence of vitamin B12 and folate deficiency. Efforts should be made to prevent deficiency of such micronutrients in pregnant and breastfeeding mothers and their infants. Treatment can affect a child's prognosis.

Ileus due to metabolic disorders after a penetrating trauma of the leg

Ileus is a medical condition where a partial or full blockage of the bowel is present. It can be caused by conditions like obstruction, GI infections, electrolyte imbalances, kidney disease, medication, hernias and adhesions.

1339. Antibiotic Prescribing Varies among Patients with a Documented Penicillin or Cephalosporin Adverse Drug Reaction

BackgroundStudies have shown that over half of hospitalized children receive an antibiotic during their encounter, of which between 30-50% is considered inappropriate. Antibiotic prescribing is further complicated as approximately 10% of children are labeled beta-lactam allergic, resulting in the use of either broad-spectrum or suboptimal therapy. The purpose of this study was to compare antibiotic prescribing between patients with a documented ADR vs. those without using a nationwide sample of hospitalized children.MethodsWe performed a point prevalence study among 32 hospitals between July 2016-December 2017 where data were collected via chart review on pediatric patient and antimicrobial characteristics, including the indication for all antimicrobials. In additional, ADR history data were collected on which antimicrobial(s) were documented (e.g., penicillin, cephalosporins). Patients were mutually assigned into either: 1) no documented ADR; 2) penicillin ADR-only; 3) cephalosporin ADR-only; and 4) ADR for both penicillin and cephalosporin. The distribution of antibiotics were compared between the ADR groups, stratified by the indication for treatment.ResultsA total of 12,250 pediatric patients (17,929 antibiotic orders) who were actively receiving antibiotics were identified. A history of penicillin and cephalosporin ADR was documented in 5.5% and 2.8% of these patients, respectively. When compared to patients with no documented ADR, penicillin ADR patients were more likely to receive a fluoroquinolone for a SSTI infection (odds ratio [OR]: 5.6), surgical prophylaxis (OR: 18.8) or for surgical treatment (OR: 5.2) (see Figure). Conversely, penicillin ADR patients were less likely to receive first-line agents, such as narrow-spectrum penicillin for bacterial LRTI (OR: 0.08) and piperacillin/tazobactam for GI infections (OR: 0.22). Cephalosporin ADR patients exhibited similar patterns with increased use of carbapenems and fluoroquinolones when compared to patients with no ADR.Figure 1: Odds of Receiving Select Antimicrobials Among PCN ADR Patients When Compared to Non-ADR patients, by Indication ConclusionA large, nationwide sample of pediatric patients who were actively prescribed antibiotics helped identify several diagnoses where comprehensive guidelines for appropriate ADR prescribing and increased ADR de-labeling initiatives are needed to ensure optimal treatment.Disclosures Brian R. Lee, MPH, PhD, Merck (Grant/Research Support) Jason Newland, MD, MEd, FPIDS, Merck (Grant/Research Support)Pfizer (Other Financial or Material Support, Industry funded clinical trial)

Outcome of immune checkpoint inhibitor (ICI) related diarrhea/colitis (IMDC) in cancer patients with superimposed GI infections.

e15166 Background: ICI therapies have revolutionized the landscape of cancer treatment. However, their increased use has also contributed to adverse events, e.g. IMDC. Clinically it is difficult to distinguish between infectious etiology or IMDC. It is unclear whether antimicrobial treatment substantially impacts the disease course. Here, we evaluated the characteristics and outcome of IMDC in cancer patients with superimposed diarrheagenic GI infections. Methods: We retrospectively evaluated cancer patients who received ICI with clinical symptoms of IMDC and confirmed stool microbiology of E. coli or non-CMV viral infections either at the time of IMDC, or within 60 days after IMDC diagnosis at MD Anderson Cancer Center 01/2011-08/2019. We described the disease course and outcome of IMDC based on their status of GI infection and antimicrobial treatment. Results: Total 72 patients were included, among them, 50 control patients with IMDC and no GI infection, 22 had diarrheagenic infections, composed of 17 E coli pathogens: Enteropathogenic, Enterotoxigenic, Enteroaggregative, and E coli 0157:H7 serotype; and 5 viral etiologies: Adenovirus, Norovirus, and Sapovirus. Patients in the infection group had higher grade of colitis (42.9% vs 18.4%, P = 0.041), and more frequent hospitalization (86.4% vs 62%, P = 0.052). 68.2% patients in the infection group received infliximab/vedolizumab add-on treatment compared to 40% in the no infection group (P = 0.078). Patients with GI infection and antimicrobial treatment had much higher IMDC recurrence rate than no antimicrobial treatment (50% vs 0, P = 0.015). GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. Conclusions: IMDC can occasionally be complicated by infection from common GI pathogens. Antimicrobial treatment was mostly used in severe IMDC cases and did not circumvent the need for immunosuppressant or improve the clinical outcomes. GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. [Table: see text]

HLA Matched Sibling Donor (MSD) Bone Marrow Transplantation (BMT) for Children with Limited Financial Resources in a Government Hospital (Maharaja Yashwantrao Holker Hospital [MYH]) in Indore, India: A Collaborative Project between East and West.

<h3>Introduction</h3> In India, most MSD-BMTs are conducted in private hospitals and are associated with a cost of $20-30,000, which most poor families cannot afford. To serve children with limited financial resources (below the poverty line or with a yearly family income of <$7,000), we have developed a BMT unit at MYH in Indore, India. <h3>Methods</h3> Collaboration Model- Figure <h3>Team</h3> Two general pediatricians were trained for 6 months at Columbia University, NY, where they developed SOP and protocols. <h3>Blood Bank</h3> Able to provide PRBC and platelets, could perform plasma but no RBC depletion. <h3>Patient Recruitment</h3> HLA typing camps were conducted in 5 cities, 253 families were typed, 72 pts had 10/10 HLA MSD. DKMS Germany performed HLA typing free of cost. <h3>Financial Support</h3> To provide free BMT, Airport Authority of India and Bina Refinery provided financial support through corporate social responsibility. <h3>Conditioning Regimen</h3> Majority of patients (pts) received r-ATG-6mg/kg, FLU-150mg/m², BU-12.8-16mg/kg (without PK studies) and cytoxan-200mg/kg. Prophylaxis; aGVHD: CSA/MTX. Acyclovir until day 100. Fluconazole until ANC >1000/mm³. Bactrim for PCP. G-CSF was not routinely administered. <h3>Follow-Up</h3> Pts stayed in the hospital vicinity for up to 6 months post-BMT. The majority of outpatient medications were also provided free of charge. <h3>Results</h3> Donors: 13F and 7M, median age 8 yrs (2-18). The median number of CD34+ cells harvested from bone marrow was 5.5 × 10⁶/kg (1.5-21.6); only 2 donors were G-CSF mobilized. <h3>Patients</h3> First BMT was conducted in April 2018. Median FU 9 months (3-17). Of the first 20 pts, 12 were males. Pts were ages 2-5Y (n=9), 5-10Y (n=8) and >10Y (n=3). 19/20 pts were heavily transfused. Thalassemia spectrum (16/20), SCD (n=1), MDS (n=1), SAA (n=1), and CML (n=1). 4 pts with major ABO incompatibility underwent RBC desensitization. Median time for ALC >500/mm³, neutrophil and platelet engraftment was 19d (12 -30), 27d (14-33) and 25d (15-50), respectively. Two pts had graft failure (one died). At last follow up, two pts have stable mixed chimerism and 16 (80%) have donor chimerism >90%, all 18 engrafted pts are transfusion independent. Overall survival is 95%. The median cost of BMT was $11,000 ($6,000-22,000). <h3>Conclusion</h3> Early results demonstrate the feasibility of our model. With appropriate remote supervision and dedicated general pediatricians and nurses with limited BMT training, we can successfully conduct MSD BMT in a resource-constrained set up. Despite living in remote villages, poverty, facing socio-cultural challenges, families can be trained to provide appropriate care at home. Multi-drug resistant bacteraemia and GI infections remain a major concern.

Prevention of infective endocarditis and bacterial resistance to antibiotics: A brief review.

The purpose of this statement is to debate the recommendations of the American Heart Association (AHA) for the prevention of infective endocarditis through an antibiotic prophylaxis protocol and its relation with bacterial resistance to antibiotics. Since dental infections involve biofilms that include several bacterial species (Gram-negative and Gram-positive), it is essential, from the dental point of view, to consider the frequency, magnitude, and duration of bacteremia associated with active dental infections before applying antibiotic prophylaxis. The actual guidelines for antibiotic prophylaxis should be revised according to recent evidence of bacterial resistance. Amoxicillin/clavulanic acid and moxifloxacin should be considered due to their effectiveness against bacteria associated with oral, GU, and GI infections and the low rates of antibiotic resistance associated with these antibiotics, instead of the actual protocol, which includes amoxicillin (2g) or clindamycin (600mg) administered an hour before the dental procedures. The breaking point to test the antibiotic bacterial resistance (ABR) had a wide range in the different studies that were analyzed, which could explain the widely varied ABR percentages reported for the various antibiotics used for antibiotic prophylaxis.

Molecular characterization of norovirus infection responsible for acute diarrhea in Congolese hospitalized children under five years old in Brazzaville, Republic of Congo

BackgroundAcute diarrhea is a leading cause of morbidity and mortality among children under five worldwide. As no published data is available on the occurrence of this infection in the Republic of Congo, this study aimed at (1) determining the prevalence and (2) characterizing genotypes of norovirus strains in Brazzaville. MethodsFrom June 2012 to June 2013, stool samples were collected from hospitalized young children with acute gastroenteritis. A total of 545 samples were tested for GI and GII norovirus infections using nested duplex reverse-transcription–polymerase chain reaction and sequencing. ResultsThe GI and GII norovirus infection were detected in 148 samples. Males (28%) were not significantly more infected than females (25%). Norovirus infection was found exclusively in children aged under 24 months with a higher prevalence (P=0,048) in the age group of 7–12 months, and throughout the year with a peak in August and September. Genetic diversity of norovirus strains revealed that GII was the most prevalent (87%). No risk factor was significantly associated with norovirus infection. ConclusionThis study showed that noroviruses are important agents responsible for acute diarrhea in Congolese children and highlights the importance of continued surveillance.