FMT for Lung and Associated-organ Rescue Efficacy in Pulmonary Infection With MDROs (FLARE-PM)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Status: Enrolling

Conditions: Lung Infection; Food Intolerance Syndromes; Microbial Colonization

Treatments: Other: Fecal suspension

Study type: Interventional

Funder types: Other

Identifiers

NCT06970262

0928-01

Details and patient eligibility

About

Currently, lung infections caused by multidrug-resistant organisms (MDROs) represent a significant global health burden. In the intensive care unit (ICU), the administration of antibiotics, opioids, proton pump inhibitors (PPIs), vasoconstrictors, and parenteral nutrition-combined with the underlying severity of critical illness-leads to profound disruption of the gut microbiota, which may concurrently impair pulmonary microecology and negatively influence long-term patient outcomes. Although pulmonary microecology has garnered increasing scientific attention, the potential causal link between gut dysbiosis and the development of pulmonary microbial imbalance remains poorly elucidated. As such, it is currently unclear whether gut dysbiosis in patients with MDRO-related pulmonary infection contributes to or exacerbates pulmonary microecological disturbances. This study aims to characterize differences in gut microbiota composition and pulmonary microecology between ICU patients with and without MDRO-associated pulmonary infection, and to investigate the association between alterations in gut microbiota and changes in the pulmonary microbial environment.

Fecal microbiota transplantation (FMT) is a therapeutic intervention involving the transfer of functionally intact microbial communities from healthy donors to recipients, with the objective of restoring a disrupted gut microbiota and treating both gastrointestinal and systemic conditions. Evidence suggests that FMT effectively reduces intestinal colonization by MDROs and prevents secondary infections in non-ICU populations. Over the past decade, FMT has demonstrated transformative potential in managing refractory intestinal and extra-intestinal diseases, offering a novel, mechanism-driven strategy for modulating host microbial ecosystems. These findings indicate that FMT not only facilitates the restoration of a balanced gut microbiota but may also reduce recurrent infections by suppressing the proliferation of drug-resistant bacterial strains. Given that gut-resident microorganisms serve as a major reservoir for enterogenic infections, hospital-acquired bacteremia, and ventilator-associated pneumonia, this project will conduct a prospective, randomized controlled trial (RCT) in critically ill patients admitted to the ICU with pulmonary infection-specifically targeting those eligible for antibiotic de-escalation and exhibiting clinical features of food intolerance syndrome. FMT will be administered via a nasojejunal tube to correct gut dysbiosis induced by broad-spectrum antimicrobials and other iatrogenic factors. The primary objectives are to evaluate the efficacy and safety of FMT in promoting the restoration of pulmonary microbial homeostasis and to assess its impact on clinically relevant outcomes, including length of stay in the ICU, ICU mortality, in-hospital mortality, and 28-day all-cause mortality.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

The initial step involves characterizing alterations in the pulmonary and intestinal microbiota among ICU patients with pathogen-associated infections, including multidrug-resistant organisms (MDROs), and examining the associations between these microbial changes.

Inclusion Criteria:

1. Age ranging from 18 to 70 years old;
2. Gender and ethnicity are not restricted;
3. Informed consent obtained.

Exclusion Criteria:

1. Airway antibiotics (administered via nebulization or intravenous infusion) have been utilized since the current hospitalization;
2. Pulmonary infection caused by non-bacterial pathogens, such as viruses, fungi, or atypical organisms;
3. Infections located outside the pulmonary system, including those in the bloodstream, abdominal cavity, or urinary tract;
4. Respiratory failure secondary to non-pulmonary infections, such as cardiogenic factors or sepsis-like syndromes;
5. Chronic pulmonary conditions, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, and pulmonary interstitial fibrosis;
6. Chronic gastrointestinal disorders, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and non-alcoholic fatty liver disease (NAFLD);
7. Recent surgical procedures involving the abdomen or lungs (within 14 days prior to admission);
8. Pregnant or lactating individuals；
9. Subjects who participated in other clinical studies as trial participants at the time of enrollment or within 3 months prior to enrollment；
10. Lack of a signed written informed consent form.

Further trial will be conducted to investigate the effect and safety of FMT on the recovery of pulmonary microecological imbalance in critically ill patients, and to evaluate its impact on the length of stay in the ICU, ICU mortality, in-hospital mortality, and 28-day mortality, etc.

Inclusion Criteria:

1. Age 18-70 years, regardless of gender or ethnicity;
2. ICU admission ≥24 hours;
3. Expected ICU stay ≥7 days;
4. Mechanically ventilated patients with confirmed pulmonary MDRO infection prior to enrollment. Target MDRO has available narrow-spectrum antibiotics; if the pathogen is pan-resistant (e.g., pan-drug-resistant Acinetobacter baumannii) and treatment relies solely on polymyxins or other limited options, exclusion is required. The attending physician must confirm that short-term discontinuation of broad-spectrum antibiotics is safe;
5. Written informed consent provided.

Exclusion Criteria:

1. Severe systemic infection during early resuscitation, with hemodynamic instability, severe tissue hypoperfusion, or major electrolyte and acid-base disturbances;
2. High risk of death within 5 days per clinician assessment, or presence of treatment-limiting directives;
3. Active gastrointestinal bleeding or perforation indicating severe intestinal barrier damage;
4. Inability to tolerate enteral nutrition supplying ≥50% of caloric needs due to fibrotic bowel stenosis or high-output fistula;
5. Planned or recent abdominal surgery (within 14 days before enrollment);
6. Diagnosed fulminant colitis or toxic megacolon;
7. Neutropenia (absolute neutrophil count < 1500 cells/µL);
8. Congenital or acquired immunodeficiency;
9. Recent use of high-risk immunosuppressive or cytotoxic agents: e.g., rituximab, doxorubicin, or corticosteroids ≥20 mg/day prednisone equivalent for ≥4 weeks;
10. Pregnant or breastfeeding individuals;
11. Enrollment in another clinical trial within 3 months before or at study entry.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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150 participants in 2 patient groups

FMT intervention group

Experimental group

Description:

On the basis of the standard ICU treatment protocol, FMT was administered via a nasojejunal tube. Over three consecutive days, 50-100 ml of intestinal flora suspension was delivered through the nasojejunal tube daily between 11:00 and 13:00. A strict antibiotic intervention window spans 24 hours before to 48 hours after FMT infusion. During this period, narrow-spectrum antibiotics active against confirmed pulmonary target MDROs (based on susceptibility testing) may continue to ensure effective infection control and patient safety. All broad-spectrum antibiotics should be stopped unless they are the only effective option. Empiric or prophylactic antibiotics without confirmed infection are prohibited. Oral vancomycin, metronidazole, and microbiota-disrupting quinolones should be avoided, except when intravenous quinolones are required for MDRO treatment. Antifungals may continue due to minimal impact on gut bacteria.

Treatment:

Other: Fecal suspension

Control group

No Intervention group

Description:

Receiving the standard ICU treatment protocol involves a comprehensive set of systematic and standardized medical and nursing interventions designed for critically ill patients in the ICU. These interventions are aimed at ensuring patient stability through multidisciplinary collaboration, continuous physiological monitoring, and functional support, while also facilitating recovery. The ICU treatment protocol is developed based on modern medical principles and extensive clinical experience, encompassing all aspects from fundamental care to advanced life support. The control group follows the same antibiotic rules during the same window but receives placebo. This ensures comparable anti-infective treatment intensity between groups.