BACKGROUND:There is little data on gut microbiome and various factors that lead to dysbiosis in pediatric intestinal failure (PIF). This study aimed to characterize gut microbiome in PIF and determine factors that may affect microbial composition in these patients.METHODS:This is a single-center, prospective cohort study of children with PIF followed at our intestinal rehabilitation program. Stool samples were collected longitudinally at regular intervals over a 1-year period. Medical records were reviewed, and demographic and clinical data were collected. Medication history including the use of acid blockers, scheduled prophylactic antibiotics, and bile acid sequestrants was obtained. Gut microbial diversity among patients was assessed and compared according to various host characteristics of interest.RESULTS:The final analysis included 74 specimens from 12 subjects. Scheduled prophylactic antibiotics, presence of central line associated bloodstream infection (CLABSI) at the time of specimen collection, use of acid blockers, and ≥50% calories delivered via parenteral nutrition (PN) was associated with reduced alpha diversity, whereas increasing age was associated with improved alpha diversity at various microbial levels ( P value <0.05). Beta diversity differed with age, presence of CLABSI, use of scheduled antibiotics, acid blockers, percent calories via PN, and presence of oral feeds at various microbial levels ( P value <0.05). Single taxon analysis identified several taxa at several microbial levels, which were significantly associated with various host characteristics.CONCLUSION:Gut microbial diversity in PIF subjects is influenced by various factors involved in the rehabilitation process including medications, percent calories received parenterally, CLABSI events, the degree of oral feeding, and age. Additional investigation performed across multiple centers is needed to further understand the impact of these findings on important clinical outcomes in PIF.

Pediatric intestinal failure (PIF) is a relatively rare disease entity that requires focused interdisciplinary care and specialized nutrition management. There has long been a lack of consensus in the definition of key terms related to PIF because of its rarity and a plethora of small studies rather than large trials. As such, the American Society for Parenteral and Enteral Nutrition (ASPEN) PIF Section, composed of clinicians from a variety of disciplines caring for children with intestinal failure, is uniquely poised to provide insight into this definition void. This document is the product of an effort by the Section to create evidence-based consensus definitions, with the goal of allowing for appropriate comparisons between clinical studies and measurement of long-term patient outcomes. This paper has been approved by the ASPEN Board of Directors.

BACKGROUND:Small bowel bacterial overgrowth (SBBO) is a common, but difficult to diagnose and treat, problem in pediatric short bowel syndrome (SBS). Lack of clinical consensus criteria and unknown sensitivity and specificity of bedside diagnosis makes research on this potential SBS disease modifier challenging. The objective of this research was to describe clinical care of SBBO among international intestinal rehabilitation and nutrition support (IR&NS) providers treating patients with SBS.METHODS:A secure, confidential, international, electronic survey of IR&NS practitioners was conducted between March 2021 and May 2021. All analyses were conducted in the R statistical computing framework, version 4.0.RESULTS:Sixty percent of respondents agreed and 0% strongly disagreed that abdominal pain, distension, emesis, diarrhea, and malodorous stool, were attributable to SBBO. No more than 20% of respondents strongly agreed and no more than 40% agreed that any sign or symptom was specific for SBBO. For a first-time diagnosis, 31 practitioners agreed with use of a 7-day course of a single antibiotic, with a majority citing grade 5 evidence to inform their decisions (case series, uncontrolled studies, or expert opinion). The most common first antibiotic used to treat a new onset SBBO was metronidazole, and rifaximin was the second most commonly used. One hundred percent of respondents reported they would consider a consensus algorithm for SBBO, even if the algorithm may be divergent from their current practice.CONCLUSION:SBBO practice varies widely among experienced IR&NS providers. Development of a clinical consensus algorithm may help standardize care to improve research and care of this complex problem and to identify risks and benefits of chronic antibiotic use in SBS.

BACKGROUND:Ethanol lock use has been associated with significantly lower rates of central line-associated bloodstream infection (CLABSI) in children with intestinal failure. Concerns have been raised among intestinal rehabilitation program providers regarding the impact of recent changes in cost and availability of ethanol locks in the US.METHODS:We conducted a survey among the members of the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition Intestinal Rehabilitation Special Interest Group (NASPGHAN IR-SIG) regarding practice changes among providers to tackle this issue and the anticipated effect on CLABSI rates.RESULTS:The results show that the vast majority of US participants use ethanol locks in their population with intestinal failure, with most anticipating or already experiencing reduction in access to ethanol locks. Most worrisome is that more than half of participating programs expect an increase in CLABSI rates in this vulnerable patient population as a consequence of limited access to ethanol locks.CONCLUSION:Further multicenter prospective studies to assess the efficacy of alternative locking agents, besides ethanol, are needed in order to have readily available and affordable options for CLABSI prevention in the future.

BACKGROUND:In this study, we aim to determine the effect of scheduled antibiotics on gut microbiome in pediatric intestinal failure (IF) and to evaluate the effect of the gut microbiome on nutrition outcomes in IF.METHODS:Fecal samples were collected at regular intervals from pediatric patients with IF for gut microbiome comparison between 2 cohorts: (group 1) those on scheduled prophylactic antibiotics and (group 2) those who were not on scheduled antibiotics. Gut microbiome composition and diversity were compared among the 2 cohorts. The association among gut microbiome composition, diversity, and nutrition outcomes (mainly ability to decrease parenteral nutrition [PN] energy requirement and ability to attain positive growth) was also determined.RESULTS:The microbiome of patients with IF on scheduled antibiotics differed significantly from those not on scheduled antibiotics. Abundance of certain Gram-negative and pathogenic bacteria (Pseudomonas, Prevotella, and Sutterella) was higher in the scheduled cohort. Patients with decreased Enterobacteriaceae demonstrated a greater ability to demonstrate a reduction in PN requirement, as well as attain positive growth.CONCLUSION:Scheduled antibiotics may alter the gut microbiome in children IF, which in turn may have an influence on important nutrition outcomes in pediatric IF. Further larger, multicenter studies are needed to determine the effect of scheduled antibiotics on the gut microbiome in this patient population and their overall effect on nutrition outcomes.

Background Central line associated bloodstream infections are a common cause of bacteremia and sepsis in pediatric patients with intestinal failure, secondary to long-term CVC use. Methods An IRB approved retrospective chart review was conducted on TPN-dependent patients with IF who had an identified CLABSI and presented to Children's of Alabama's emergency department (ED) and were admitted to the hospital. Results Forty-four patients were included in the study, 28 in the first 18-month period and 26 in the second, with 10 in both populations. After implementation, mean time from ED presentation to antibiotic ordered and ED admission to antibiotic administered were lower. Mean time between antibiotic administration and admission to the floor was greater, and number of infectious disease consultations was greater. Floor-ICU transfers were lower, readmissions within 30 days was similar, and mean length of stay was similar. Conclusion A collaborative, multidiscipline-supported protocol for the care of patients with IF presenting to the ED enhances efficiency of antibiotic ordering/administration, as well as reduces the number of unplanned floor-ICU transfers.

BACKGROUNDThe coronavirus disease 2019 (COVID-19) pandemic has influenced how healthcare is being provided, particularly in patients whose diagnoses require multidisciplinary care, such as pediatric intestinal failure (IF). We sought to ascertain the effects of the COVID-19 pandemic on healthcare delivery for pediatric patients with IF.METHODSA 20-question survey was administered to members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation (IR) Special Interest Group. Input values were "yes" and "no," along with a free-text response. Following a 10-day open survey period, data were divided into cohorts based on patient population size and disease burden by state. Analysis was then performed using the χ2 test application.RESULTSResponses from 29 centers were included in analysis. Centers that followed >50 patients on parenteral nutrition (PN) were more likely to have social workers present in telemedicine visits and observed more central line difficulties among families. Centers located in states with <40,000 reported cases of COVID-19 saw patients less frequently and were more likely to withhold changes to PN prescriptions. Additionally, the survey revealed a significant degree of financial hardship and food insecurity among families.CONCLUSIONMany aspects of pediatric IF healthcare delivery have been impacted by the COVID-19 pandemic, both for care providers and caregivers. Despite the availability of telemedicine, IR centers should remain attentive to the global needs of the pediatric IF patient, as well as their families.

To the Editor: We wish to update the pediatric gastroenterology community on a critical issue for children with intestinal failure (IF) that threatens to increase emergency department visits and hospitalizations during the pandemic related to SARS-CoV-2. Intestinal rehabilitation (IR) programs seeking to protect their vulnerable patients from COVID-19 are taking unprecedented steps to minimize healthcare exposure, efforts undermined by the recent price increase, and shortage of sterile ethanol. Children with IF are dependent on central venous catheters for parenteral fluids and nutrition (PN), risking central line-associated blood stream infection (CLABSI), sepsis, liver injury, and death. Locking the central venous catheter with ethanol, a frequently studied and beneficial intervention in IR, reduces the CLABSI rate by 63% (6 infections per 1000 catheter days) (1). Belcher Pharmaceuticals received FDA approval with orphan drug designation for Ablysinol (dehydrated alcohol) for adult heart disease (2). Such designation precludes medical marketing by others until 2025 and recently resulted in shortage and almost 8-fold price increase (3). On March 29, 2020, we notified the FDA of a national survey of IR programs on the impact of this decision to IF patients in North American. Twenty centers from 14 US states caring for approximately 950 patients receiving home PN responded. All programs prescribed ethanol with the majority (18, 90%) prescribing 70% concentration. Frequency of use was evenly split between daily (10, 50%) and thrice weekly (10, 50%). Recent shortage was experienced by 17 (85%) centers and 15 (75%) had been requested or mandated to change prescribing practices by homecare agencies due to cost or shortage. This is particularly concerning as a reduction in ethanol lock frequency during a previous shortage resulted in “complete failure” in prophylaxis (4). There is a need to rapidly regain access to ethanol or other agents used internationally, such as 4% tetrasodium ethylenediaminetetraacetic acid or taurolidine citrate. Both are efficacious antimicrobials and may offer other desirable benefits such as anticoagulation (5,6). Always important, the prevention of CLABSI and ensuing hospitalization and resource utilization is ever more relevant while a highly transmissible infectious disease ravages our health care system.

Gastrosplenic fistula is a very rare entity, most commonly occurring as a distinctive complication of splenic or gastric malignancies, most notably diffuse large B cell lymphoma (DLBCL). Benign gastric ulcer, splenic abscess, and Crohn's disease have also been reported as possible causes. We report a nonmalignant case of 16-year-old male with a gastrosplenic fistula of unclear etiology. The fistulous tract was confirmed by an upper endoscopy and an upper gastrointestinal series. Subsequently, it was surgically managed with a subtotal gastrectomy with "Roux-en-Y" reconstruction and a feeding jejunostomy.

Background/Purpose: Although pediatric intestinal failure (IF) is now a survivable diagnosis, children are still at risk for complications. Loss of venous access persists as a leading indication for intestinal transplantation. The goal of this study was to identify risk factors for loss of venous access in a pediatric intestinal failure population on long-term PN. Methods: We identified all patients who were PN dependent. Results: Patients that developed venous thrombosis had significantly more lines placed in the first 2 years of life compared to those who did not develop thrombosis. Multivariate regression analysis revealed that diagnosis (NEC and gastroschisis) and parental education were significant predictors of venous thrombosis. Conclusion: By identifying potential risk factors for thrombus development, interventions can be developed to improve the overall outcome in pediatric IF patients. Type of Study: Diagnostic (C) 2018 Published by Elsevier Inc.

BACKGROUND We sought to evaluate the relationship between determinants of intestinal failure (IF) and achieving enteral autonomy from parenteral nutrition (PN) in a large single-center cohort of children. METHODS This is a retrospective chart review of pediatric subjects enrolled in a database for the Center for Advanced Intestinal Rehabilitation at Children's of Alabama from 1989 to 2016. IF was defined as dependence on PN for >60 days. Subjects were included if they were followed since birth or infancy for a minimum of 3 months and sufficient documentation of study variables were available. Gestational age, race, diagnosis, anatomy (percent small and large bowel remaining, presence of ileocecal valve [ICV]), county of residence (rural/urban), and days of PN use were recorded. Kaplan-Meier curves and parametric survival regression models were used to investigate the relationship between the demographic and clinical variables with the length of PN use. RESULTS Initially, 290 subjects were available to review. After inclusion/exclusion were applied, 158 subjects remained. Gestational age, diagnosis (necrotizing enterocolitis), small-bowel length (>50%), and presence of an ICV were all positive predictors for reaching enteral autonomy. Residual colon length was associated with shorter duration of PN in days. CONCLUSION Enteral autonomy is a key outcome among children with IF. In our cohort, we found that gestational age, diagnosis, remaining small bowel, and presence of ICV are positive predictors for reaching this important milestone. Colon length is also an important factor with respect to duration of PN in days.

Children with intestinal failure often require long-term central venous access for parenteral nutrition. Line-related complications often include liver dysfunction, sepsis, and loss of venous access. Osteomyelitis is a rare complication that has been reported in adults with intestinal failure. There has been little focus, however, on the development of osteomyelitis in the pediatric population. In this study we present 2 case studies of patients with intestinal failure requiring parenteral nutrition who subsequently developed acute osteomyelitis.

BACKGROUND:We determined qualitative and quantitative serum unconjugated bile acid (SUBA) levels among children with history of intestinal failure (IF) and suspected small bowel bacterial overgrowth (SBBO). METHODS:This was a single-center, case-control pilot study conducted at Cincinnati Children's Hospital Medical Center. Children with history of IF and suspected SBBO were enrolled as subjects. Age-matched children without IF or suspected SBBO served as controls. All participants underwent small bowel fluid sampling for microbial culture analysis. Additionally, serum fractionated and total bile acids were measured by liquid chromatography-mass spectrometry at enrollment and following treatment for SBBO. RESULTS:SUBA concentrations were elevated in IF subjects (median 1.16 μM, range 0.43-10.65 μM) compared with controls (median 0.10 μM, range 0.05-0.18 μM, P = 0.001). Among SUBA, chenodeoxycholic acid (CDCA) was significantly elevated in subjects (median 0.8 μM, range 0-7.08 μM) compared with controls (median 0 μM, range 0-0.03 μM, P = 0.012). When controls were excluded from analysis, IF subjects with positive aspirates for SBBO demonstrated higher concentration of CDCA (median 7.36 μM, range 1.1-8.28 μM) compared with IF subjects with negative aspirates (median 0.18 μM, range 0-1.06 μM, P = 0.017). Treatment for SBBO did not alter SUBA concentration. CONCLUSIONS:SUBA concentrations are elevated in children with history of IF and presumed SBBO compared with non-IF controls. CDCA was more prevalent in IF subjects with positive aspirates for SBBO compared with IF subjects with negative aspirates. The determination of SUBA concentration may be a useful surrogate to small bowel fluid aspiration in the diagnosis of SBBO in children with history of IF.

Background. No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model.Methods. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 x 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 x 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration.Results. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (>= 3.0 L) to severe (>= 5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P<.0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P<.0001).Conclusions. The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine.

Galloway, David P. MD; Wallihan, Daniel MD; Smith, Milton T. MD; Abu-El-Haija, Maisam MD Author Information

Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post‐transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream.

BACKGROUNDCentral line-associated bloodstream infections (CLABSIs) pose a significant challenge in the lives of patients with intestinal failure (IF). We hypothesized that plasma immunoglobulins against flagellin (FLiC) and lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial febrile episodes and that levels would increase with infection and decline following appropriate antibiotic treatment.MATERIALS AND METHODSPatients with IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age, were recruited at Cincinnati Children's Hospital Medical Center. Anti-FLiC and anti-LPS plasma antibody levels were measured in 13 children with IF at baseline, during febrile events, and also following treatment with antibiotics. These were also measured in 11 healthy children without IF who were recruited as controls.RESULTSPlasma anti-FLiC IgA levels increased during febrile episodes in all patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical density units, respectively; P = .046). Neither plasma anti-FLiC nor anti-LPS IgA or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared with baseline levels. Compared with controls, patients with IF had significantly higher plasma levels of anti-FLiC and anti-LPS IgA at baseline.CONCLUSIONPlasma anti-FLiC IgA antibody levels rise during febrile episodes but do not differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF. However, the upregulation of these antibodies in IF suggests the baseline systemic presence of Gram-negative bacterial products.