Prevention and Decolonization of Multidrug-resistant Bacteria With Probiotics

Prevention and Decolonization of Carbapenemase-producing Enterobacteriaceae With Probiotics

This study explores the effect of probiotic administration to decrease colonization by Carbapenem resistant Enterobacteriaceae (CRE) in at-risk populations. Colonized patients will be randomized to receive probiotics or placebo for 14 days and reevaluated for colonization in follow up.

Study Overview

• Status: Unknown
• Conditions: Probiotics; Enterobacteriaceae Infections
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

Detailed Description

The use of antibiotics is known to have significant effects on the intestinal microbiota. Studies have linked this alteration with the risk of colonization and / or infection by Carbapenem resistant Enterobacteriaceae (CRE) and / or Clostridium difficile (Cd). The impact of these microorganisms has been demonstrated, with mortality rates in inpatients of around 30-50% for patients infected with CRE and 10% in Cd. It is necessary to implement mechanisms to contain dissemination and decrease colonization, in order to prevent infections caused by such agents.

Probiotics are foods consisting of live microorganisms and could restore the balance of the microbiota and avoid colonization by multi-resistant germs. Systematic reviews have shown a protective effect of probiotics for Cd. Studies on the effect on CRE are scarce and have been related mostly to prevention of colonization. Among the probiotics obtained by bacterial fermentation technology and already available in pharmacopoeia we have Bioflora ®. The objective of this trial is to explore the effect of probiotic consumption to decrease the duration of the colonization by CRE by comparing the percentage of patients colonized with CRE after the administration of probiotics and in the untreated group.

Methodology: Randomized clinical trial, single center. Known CRE colonized patients will be randomized to consume probiotics for 14 days or placebo. Then the colonization will be evaluated by means of anal swabs as indicated by the hospital standards with a follow up of 12 weeks from the initial intervention.

If the patient is discharged, home follow-up will be scheduled to supervise the intake of the dietary supplement and the control swabs.

The expected impact is to accelerate the process of decolonization of multi-resistant germs through the administration of probiotics leading to a shorter contact isolation time in and reducing the risk of complications in CRE colonized patients.

• Study Type: Interventional
• Enrollment (Anticipated): 228
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria I Staneloni, MD; Phone Number: 1536670333.; Email: maria.staneloni@hospitalitaliano.org.ar
• Study Contact Backup: Name: Sol Burokas, MD; Phone Number: 8165 541149590200; Email: maria.burokas@hiba.org.ar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CRE- colonized patients
• adult patients in hospital (over 18 years old)
• Part of the HIBA health care plan
• CRE positive rectal swab or stool in the last 14 days

Exclusion criteria:

• Enteral route enabled (oral, nasogastric tube, gastrostomy or jejunostomy)
• Refusal to participate in the study
• Not available for weekly checks, minimum up to 12 weeks from enrollment
• Clostridium difficile active infection concomitant with CRE swab in a 14-day period days
• Neutropenia G3 or greater (less than 1000 neutrophils at the time of enrollment).
• Severe immunosuppressed at the time of recruitment according to the CDC definition (patients transplanted, HIV with CD4 <200, congenital immunodeficiencies, leukemias, lymphomas, cancer disseminated, current chemotherapy or radiotherapy, treatment with corticoids high dose:prednisone 20 mg / d> 2 weeks or immunosuppressive drugs).
• Patient with valvular prostheses
• Imminent death
• Fistula or dehiscence of the gastrointestinal tract
• Acute pancreatitis
• Patient of critical units in ileus and / or with high requirement of vasopressors (noradrenaline equal to or greater than 0.5 gammas) at the time of recruitment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic isolated intestinal bacteria (active); Patients randomized to active arm, will consume 5ml every 12 hours per day of a suspension of probiotics (Bioflora ® Lactobacillus casei, Lactobacillus plantarum, Streptococcus faecalis y Bifidobacterium brevis) for 14 days.The content of each bottle is reconstituted up to 50 ml (10 doses) with drinking water The prescription of the intervention will be carried out and monitored through the electronic medical record. In the hospital setting, the probiotic is reconstituted by the nursing staff. If the patient is discharged before this period the patient and family will be instructed to perform the reconstitution at home.	Dietary supplement: Probiotic; Intervention: defined as probiotic consumption
Placebo Comparator: Placebo; Patients randomized to the placebo arm, will consume 5ml every 12 hours per day of a suspension of placebo for 14 days. The prescription of the intervention will be carried out and monitored through the electronic medical record.	Dietary supplement: Placebo; Placebo consumption. The placebo will be provided by the company that produces the probiotic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
presence of CRE in anal swab or stool culture in follow-up control:	CRE anal swab positive upon discharge, therapeutic adjustment or in-hospital death. ● Date of swab, therapeutic adjustment or in-hospital death. and within a month : ● Control CRE swab per month for KPC: Categorical binomial: Positive / Negative. Will be performed 30 days after enrollment and weekly for 8 weeks if positive. It will be considered negative when the patient as three consecutive negative swabs separated by a week. It will be persistently positive when during this period of follow-up at least one of the swabs is positive, total follow-up 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
positive for clostridium difficile diarrhea	If a patient develops diarrhea at some point during hospitalization, screening for Cd will be performed at the attending phisician´s discretion If the patient has diarrhea with a positive Cd toxin and is receiving probiotic he/she should leave the study and the data for CRE will be evaluated with the last available swab at the time of the exit event (positive for clostridium difficile diarrhea).	12 weeks

Collaborators and Investigators

• Sponsor: Hospital Italiano de Buenos Aires

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: February 3, 2019
• First Submitted That Met QC Criteria: May 27, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: probiotics; Carbapenemase-producing Enterobacteriaceae
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections
• Other Study ID Numbers: 3738

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No