Clinical trial NCT06485791: Evaluation of the Variation of the Intestinal Microbiota and the Integrity of the Intestinal Barrier in Patients With M.D.R. Germ-induced Pneumonia Undergoing Enteral Nutrition
Official title: Evaluation of the Variation of the Intestinal Microbiota and the Integrity of the Intestinal Barrier in Patients With M.D.R. Germ-induced Pneumonia Undergoing Enteral Nutrition
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Multi Drug Resistant
Dysphagia
Keywords: Antibiotic resistance
Enteral nutrition
Lead sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Sponsor class: OTHER
Collaborators: name: Russo Francesco, MD
name: Rossella Donghia, Biologist
name: Maria Notarnicola, Clinical Pathology Director
name: Pasqua Letizia Pesole, Biologist
name: Sergio Coletta, Laboratory Technician
name: Anna Ancora, Laboratory Technician
name: Francesco Gabriele, Intensive Care Unit Director
First posted: 2024-07-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll patients who will be hospitalized in the U.O.C. of Anesthesia and Intensive Care of our institution, after having been admitted to other hospitals following a traumatic event which required mechanical ventilation.

Following tracheostomy, patients developed an infection. The infection was subsequently treated with high doses of various antibiotics which led to the onset of pneumonia caused by M.D.R. germs.

Once the overall clinical picture has stabilized, i.e. the specialist needs have ceased, patients come to the U.O.C. of Anesthesia and Intensive Care Unit with a clinical picture compromised by the use of antibiotics, which caused a modification of the intestinal bacterial flora and microbiota. Therefore they are hospitalized to proceed with nutritional rehabilitation using Enteral Nutrition, as they are very often dysphagic and therefore unable to feed themselves independently, and consequently "wash out" of antibiotics from the moment of transfer.

Brief summary: The study aims to evaluate the effects of enteral nutrition in subjects with MDR on the intestinal microbiota

Detailed description: The M.D.R. it is defined as multiple resistance to antibiotics and its prevalence in intensive care units (ICU) is continuously increasing throughout the world, with great variability between continents, but also between the microorganisms themselves involved. It is estimated that global mortality attributable to antibiotic resistance is approximately 1.3 million deaths/year.

The study in question is a prospective observational study in which the effect of enteral nutrition in patients suffering from MDR on the intestinal microbiota will be evaluated. This study will enroll patients who will be hospitalized at the Resuscitation Center in the U.O.C. of Anesthesia and Resuscitation and Intensive Care of our institution, after having been admitted to other hospitals following a traumatic event which required mechanical ventilation.

Following tracheostomy, patients developed an infection detected by tracheobronchial aspirate The infection was subsequently treated with high doses of various antibiotics which led to the onset of pneumonia caused by M.D.R. germs.

Once the overall clinical picture has stabilized, i.e. the specialist needs have ceased, patients come to the U.O.C. of Anesthesia and Intensive Care Unit with a clinical picture compromised by the use of antibiotics, which caused a modification of the intestinal bacterial flora and microbiota. In fact, these patients present soft or liquid stools, as well as persistent diarrhea. Therefore they are hospitalized to proceed with nutritional rehabilitation using Enteral Nutrition, as they are very often dysphagic and therefore unable to feed themselves independently, and consequently "wash out" of antibiotics from the moment of transfer.

As per normal clinical practice, enteral nutrition is started for these patients to avoid the risk of malnutrition. For the purpose of standardizing the study, three different commercial formulations of enteral nutrition are used depending on the presence or absence of concomitant pathologies:

* Jevity Plus from the Abbot company for patients who do not have prevalent pathologies;
* Oxepa from the Abbot company for patients presenting with acute pneumonia;
* Novasource Gi Balance from the Nestlé company for diabetic patients in whom glycemic control is necessary due to diabetes mellitus.

Treatment with enteral nutrition lasts 10 days, at the end of which patients are discharged or, alternatively, leave the study.

For this study, the investigators will collect stool, urine, and serum samples for analysis of the fecal microbiota and metabolome and assessment of intestinal barrier integrity.

After signing the informed consent by the patient or by a close relative/legal representative (in the hypothesis that the patient is incapable of signing the consent), the investigator will proceed with the collection of the samples.

The samples will be collected at V0 upon admission, i.e. before starting artificial enteral nutrition, and at V1, i.e. after 10 days of enteral nutritional administration.

Eligibility criteria: Inclusion Criteria:

* Patients admitted to the Intensive Care Unit suffering from lung infections caused by M.D.R. germs.

Exclusion Criteria:

* Patients hospitalized with other pathologies

Primary outcomes:
measure: Composition of the microbiota
timeFrame: at Baseline and after 10 days
Secondary outcomes:
measure: Evaluation of the integrity of the intestinal barrier
timeFrame: at Baseline and after 10 days
Other outcomes:
Locations:
Study officials:
affiliation: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
name: Nicola Cappellano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Han Y, Zhang J, Zhang HZ, Zhang XY, Wang YM. Multidrug-resistant organisms in intensive care units and logistic analysis of risk factors. World J Clin Cases. 2022 Feb 26;10(6):1795-1805. doi: 10.12998/wjcc.v10.i6.1795.
citation: Kent AG, Vill AC, Shi Q, Satlin MJ, Brito IL. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat Commun. 2020 Sep 1;11(1):4379. doi: 10.1038/s41467-020-18164-7.
citation: Dubourg G, Lagier JC, Robert C, Armougom F, Hugon P, Metidji S, Dione N, Dangui NP, Pfleiderer A, Abrahao J, Musso D, Papazian L, Brouqui P, Bibi F, Yasir M, Vialettes B, Raoult D. Culturomics and pyrosequencing evidence of the reduction in gut microbiota diversity in patients with broad-spectrum antibiotics. Int J Antimicrob Agents. 2014 Aug;44(2):117-24. doi: 10.1016/j.ijantimicag.2014.04.020. Epub 2014 Jun 14.