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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Dysphagia; Multi Drug Resistant

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Nicola Cappellano, MD; Phone Number: 0804994111; Email: nicola.cappellano@irccsdebellis.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the microbiota	Improvement in the composition of the intestinal microbiota. Characterization of the microbiome will be carried out using a DNA metabarcoding and shotgun metatranscriptomics approach. DNA metabarcoding analysis will be conducted using the V5-V6 hypervariable regions of 16S rRNA for bacteria (MiSeq-Illumina platform). Samples found significant at DNA metabarcoding analysis will be subjected to metatracriptomic analysis (NextSeq 500 platform-Illumina). Metagenomic and metatracriptomic data will be analyzed using bioinformatics pipelines.	at Baseline and after 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the integrity of the intestinal barrier	Improved intestinal barrier function and integrity, assessed by measuring fecal zonulin and indole and skatole by elisa technique	at Baseline and after 10 days

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
• Collaborators: Russo Francesco, MD; Rossella Donghia, Biologist; Maria Notarnicola, Clinical Pathology Director; Pasqua Letizia Pesole, Biologist; Sergio Coletta, Laboratory Technician; Anna Ancora, Laboratory Technician; Francesco Gabriele, Intensive Care Unit Director
• Investigators: Principal Investigator: Nicola Cappellano, MD, Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Antibiotic resistance; Enteral nutrition
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: MDR&Microbiota

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No