Multidrug-resistant organism (MDRO)-infection represents a substantial global health burden. In the intensive care unit (ICU), the concurrent administration of antibiotics, opioids, proton pump inhibitors (PPIs), vasoconstrictors, and parenteral nutrition-compounded by the intrinsic severity of critical illness-induces profound gut microbiota dysbiosis. Accumulating preclinical and clinical evidence indicates that such intestinal dysregulation may trigger distal immunomodulatory and microbial shifts in the lung via the gut-lung axis, thereby contributing to pulmonary microecological imbalance and impairing recovery trajectories. Although pulmonary microecology has garnered increasing scientific attention, the causal and temporal relationship between gut dysbiosis and the establishment or exacerbation of pulmonary microbial dysbiosis in MDRO-infecction remains inadequately characterized. As a result, it is currently unclear whether gut dysbiosis serves as a primary pathogenic driver, a disease-amplifying factor, or a secondary epiphenomenon in the context of MDRO-infecction-associated lung injury.

Fecal microbiota transplantation (FMT) is a targeted microbiome-modulating intervention that involves the transfer of functionally diverse, minimally processed microbial communities from comprehensively screened healthy donors to restore ecological stability and functional redundancy in the recipient gut. Robust clinical data demonstrate that FMT effectively decolonizes the gastrointestinal tract of MDROs and reduces the incidence of secondary infections in immunocompetent, non-critically ill populations. Over the past decade, FMT has demonstrated reproducible efficacy in recurrent Clostridioides difficile infection and emerging promise in select extra-intestinal inflammatory conditions-highlighting its capacity as a mechanism-informed strategy for systemic host-microbe recalibration. Given the established role of the gut as a reservoir for enteric pathogens implicated in sepsis, hospital-acquired bloodstream infections, and ventilator-associated pneumonia (VAP), we propose a prospective, single-center, open-Label, randomized controlled trial (RCT) enrolling mechanically ventilated adults with MDRO-infeccted ventilated patients. The primary objective is to evaluate whether adjunctive FMT-delivered via nasojejunal tube-decrease 28-day mortality.

Inclusion Criteria:

1. Age 18-70 years, inclusive, irrespective of sex or ethnic background;
2. Admission to the intensive care unit (ICU) within 24-48 hours;
3. Anticipated ICU length of stay of ≥7 days, as determined by the attending intensivist prior to enrollment;
4. Mechanically ventilated patients with MDRO infection;
5. Provision of written informed consent by the participant or legally authorized representative.

Exclusion Criteria:

1. Severe systemic infection during early resuscitation, accompanied by hemodynamic instability, profound tissue hypoperfusion, or life-threatening electrolyte and acid-base disturbances;
2. Clinician-assessed high risk of mortality within 5 days, or presence of formal treatment-limiting directives (e.g., do-not-intubate or do-not-resuscitate orders);
3. Active gastrointestinal bleeding or perforation consistent with severe intestinal barrier dysfunction;
4. Inability to tolerate enteral nutrition providing ≥50% of estimated caloric requirements due to structural intestinal pathology-including fibrotic bowel stenosis or high-output enterocutaneous fistula;
5. Planned abdominal surgery or history of abdominal surgery within 14 days prior to enrollment;
6. Confirmed diagnosis of fulminant colitis or toxic megacolon;
7. Neutropenia defined as absolute neutrophil count < 1.5 × 10⁹/L;
8. Recent exposure to high-risk immunosuppressive or cytotoxic agents within the preceding 3 months, including but not limited to: rituximab (within 6 months), anthracyclines (e.g., doxorubicin), or systemic corticosteroids at ≥20 mg/day prednisone-equivalent dose for ≥4 consecutive weeks;
9. Pregnancy or lactation;
10. Participation in another interventional clinical trial within 3 months prior to enrollment or ongoing at the time of study entry.