Can Probiotic Vivomixx Eradicate Colonization With ESBL?

Probiotics as Intestinal Decolonization of ESBL-producing Enterobacteriaceae; a Randomized, Single Blinded, Placebo Controlled Clinical Trial

Can probiotic Vivomixx eradicate Extended Spectrum BetaLactam (ESBL) colonization in adult patients?

Study Overview

• Status: Completed
• Conditions: Antibiotic Resistant Infection
• Intervention / Treatment: Dietary supplement: Vivomixx; Dietary supplement: Placebo

Detailed Description

Infections due to extended spectrum cephalosporin-resistant Enterobacteriaceae (ESCRE) are a widely recognized public health threat. The prevalence of ESCRE is comparably low in Sweden but is steadily increasing; approximately 5 % of Swedish inhabitants are carrying ESCRE in the gut. ESCRE can lead to infections mainly from urine, abdomen and blood. These infections can be problematic to treat with current available antibiotics and represent a clinical challenge for clinicians around the world with considerable mortality and morbidity. Risk factors for acquiring an ESCRE is e.g. antibiotic treatment, trips to high prevalence countries, family member with ESCRE etc.

The duration of ESCRE carriage is not known. One Swedish study showed that ESCRE carriage can continue despite antibiotic treatment and that false negative cultures in between positive cultures are common. Since few new groups of antibiotics have been developed in the last decades, infections due to ESCRE may be increasingly difficult to treat. The possibility of ESCRE decolonization is therefore a desirable aim, in particular the more virulent enterobacteriaceae strains leading to recurrent clinical infection episodes.

Probiotics are microorganisms marketed as useful bacteria effective locally in the gut. In recent years many studies have focused on potential health benefits in a range of different gastrointestinal diseases e.g. ulcerous colitis, Crohn's disease, antibiotic associated diarrhoea where probiotics potentially have a therapeutic role4. Smaller studies have shown that probiotics possibly can bind and eliminate enteric pathogenic bacteria5-6. A small in vitro study showed that probiotics can be effective against antibiotic resistant bacteria. Larger clinical treatment studies are needed.

ESCRE constitutes a clinical problem and is largely seen in Escherichia coli and klebsiella spp. The investigator's theory is that the probiotic Vivomixx can reject ESCRE and thus decolonize the gut. Vivomixx contains eight different strains of probiotics; Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. bulgaricus, Streptococcus thermophilus and has the best documentation in clinical studies for enteric diseases of today.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Skåne
    • Helsingborg, Skåne, Sweden, 25187
      • Oskar Ljungquist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic (more than three months) ESBL colonization of the same strain as determined by
• species, phenotype and antibiogram.
• Patients must be able to swallow sachets.
• Must be able to speak and understand Swedish.
• Must have a permanent residence in Sweden.
• Must be able to sign informed consent in Swedish.

Exclusion Criteria:

• Immunosuppression (i.e. chemotheraphy, treatment with TNF-alpha-inhibitors).
• In patient care.
• immunodeficiency
• psychiatric disorder
• alcohol or substance abuse
• dementia
• Invasive catheters.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Two months of 2 sachets placebo each morning and 2 sachets each night. Each sachet of placebo contains 450 billion live bacteria.
Experimental: Probiotic; Vivomixx	Dietary supplement: Vivomixx; Two months of 2 sachets vivomixx each morning and 2 sachets each night. Each sachet of viviomixx contains 450 billion live bacteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of participants that have changed from ESBL-postitive to ESBL-negative.	Each patient included provides three faecal samples after the intervention which will be selectively cultured for ESBL. Rate of patients that have three negative ESBL cultures will be compared between the two groups.	After 12 months, the number of participants that have changed from ESBL-postitive to ESBL-negative will be assessed.

Collaborators and Investigators

• Sponsor: Lund University

Publications and helpful links

General Publications

• Ljungquist O, Kampmann C, Resman F, Riesbeck K, Tham J. Probiotics for intestinal decolonization of ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled clinical trial. Clin Microbiol Infect. 2020 Apr;26(4):456-462. doi: 10.1016/j.cmi.2019.08.019. Epub 2019 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2017-678678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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