Inulin for Infections in the Intensive Care Unit

Columbia University94 enrolled

Overview

Normal gut bacteria prevent colonization and subsequent infection with MDR organisms (MDROs) through competition for resources and other mechanisms. During critical illness, this function of the microbiome is lost and there are no current treatments to restore it. Preliminary data indicates that the prebiotic fiber inulin is safe and may alter the gastrointestinal microbiome to improve gut barrier function, decrease colonization with MDROs, and reduce downstream risk for intensive care unit (ICU)-acquired MDR infections. However, the impact of inulin during critical illness is unknown. This double-blind, randomized clinical trial will test inulin for the prevention of antibiotic resistant infections in the ICU. The trial's specific aims are to determine (1) the feasibility, tolerability, and safety of inulin in the intensive care unit; (2) the impact of inulin on gut colonization with antibiotic-resistant pathogens; and (2A/exploratory) the impact of inulin on ICU-acquired antibiotic-resistant infections.

The proposed trial hypothesizes that inulin maintains short-chain fatty acid (SCFA)-producing colonic anaerobes and that these bacteria are protective against multi-drug resistant organism (MDRO) colonization and subsequent MDR infection. Inulin, a vegetable-derived non-digestible polysaccharide is well established as the key nutrient source for SCFA-producing bacteria. Previous human studies have shown that (1) inulin increases levels of SCFA producers and SCFAs and (2) that this increase correlates with improved colonic mucosal integrity and resistance to MDR pathogens. In animal studies, inulin improves survival after pathogen challenge or injection with lipopolysaccharide. The overall aim of this clinical trial is to determine whether inulin improves gut colonization resistance against antibiotic-resistant pathogens and therefore prevents antibiotic-resistant infections in the setting of critical illness. To accomplish this, 90 critically ill adults who are receiving broad-spectrum antibiotics will be blindly randomized 1:1:1 to receive placebo, inulin 8 g twice daily, or inulin 16 g twice daily for a minimum of 7 days, with bedside follow-up extending to 30 days or hospital discharge.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

Inulin Oral SuspensionDRUG

Inulin powder, derived from chicory root and re-suspended in 250cc water Dosage will be either 8g twice a day or 16g twice a day - dissolved in 250cc sterile water, given oral or via enteric tube

Placebo Oral SuspensionDRUG

250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor

Broad-spectrum antibioticsDRUG

Standard of care treatment for infections

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Hospitalized in an eligible medical ICU 2. Age ≥ 18 years old at the time of hospitalization 3. With sepsis as defined by the Sepsis-3 (2016) consensus as a known or suspected infection with a sequential organ failure assessment (SOFA) score of ≥2 points above baseline 4. Received broad-spectrum antibiotics within the last 24 hours or ordered and pending administration 5. Able to complete enrollment within 4 hours of ICU admission for administration of the intervention within 6 hours of ICU admission Exclusion Criteria: 1. Inability to receive oral or enteric fluids 2. Inulin allergy 3. Hyponatremia (serum sodium ≤128 mEq/L) 4. Immunosuppression, defined as history of solid organ transplant or as receipt of ablative chemotherapy, steroids at the equivalent of ≥5 mg/day prednisone, antimetabolites, anti-tumor necrosis factor (TNF) α agents, calcineurin inhibitors, or mycophenolate 5. Surgery involving the intestinal lumen within 30 days or known intestinal strictures 6. Do Not Resuscitate (DNR) or Do Not Intubate (DNI) status, or "no escalation of care" orders 7. Lack capacity for consent and no appropriate Legally Authorized Representative (LAR)

Outcomes

Primary Outcomes

Within-individual Change in SCFA Producer Level

Relative abundance (i.e., proportion) of SCFA producing bacteria within each treatment group, will be assessed via 16S sequencing of rectal swabs. Modified intent-to-treat, comparing baseline vs Day 3 levels of SCFAs among those who receive one or more doses of the intervention and complete both assessments.

Time frame: Baseline and Day 3

Secondary Outcomes

Multidrug Resistant Organism (MDRO)-Gram Negative Bacteria (GNB) Colonization Status

Proportion of patients who are MDRO-GNB colonized within each treatment group, with MDRO-GNB colonization status classified categorically based on the presence or absence of methicillin-resistant Staphylococcus aureus (MRSA) or Gram negative bacteria (GNB) with third-generation cephalosporins non-susceptibility

Time frame: Day 0 and at last sample collected, up to Day 30

Vancomycin-resistant Enterococcus (VRE) Colonization Status

Proportion of patients who are VRE colonized within each treatment group, with VRE colonization status classified categorically based on the presence or absence of vancomycin-resistant Enterococcus (VRE)