Inulin for Infections in the Intensive Care Unit

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.

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 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-TNFα 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)