Evaluation of Bifidobacterium Breve PRL2020 in Preventing Antibiotic-Associated Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid
Evaluation of the Use of Bifidobacterium Breve PRL2020 in Preventing Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid Antibiotic Use: A Randomized Controlled Trial
Study Overview
Status
Conditions
Detailed Description
Antibiotic therapy, particularly with Amoxicillin and Amoxicillin/Clavulanic Acid, is widely used to treat bacterial infections in children. However, these antibiotics often disrupt the gut microbiota, leading to gastrointestinal side effects such as diarrhea, bloating, abdominal pain, and constipation. This imbalance can reduce the abundance of beneficial bacterial species, including bifidobacteria, potentially leading to long-term gastrointestinal dysbiosis.
This observational, non-profit study aims to evaluate the efficacy and safety of Bifidobacterium breve PRL2020 (Brevicillin®), a probiotic strain with demonstrated resistance to Amoxicillin and Amoxicillin/Clavulanic Acid. Prior research has shown that this strain has a high minimum inhibitory concentration (MIC) of 32-64 μg/mL, making it a promising candidate for preventing antibiotic-associated gut microbiota alterations.
The study will recruit 800 pediatric patients (ages 3-12 years) who require antibiotic therapy for infections. Participants will be randomized into two groups:
Probiotic Group: Receives Bifidobacterium breve PRL2020 (20 billion CFU per day) alongside antibiotic treatment.
Control Group: Receives antibiotics only, without probiotic supplementation. The primary outcome will be the evaluation of gastrointestinal symptoms and stool consistency using the Bristol Stool Scale and a VAS symptom scale (0-7 points) over a 15-day period (treatment duration + follow-up). The secondary outcome will assess the safety and tolerability of the probiotic intervention.
Clinical data will be collected via a daily symptom diary maintained by caregivers, including frequency of bowel movements, stool quality, presence of abdominal pain, and other potential side effects. Statistical analysis will determine whether Bifidobacterium breve PRL2020 significantly reduces antibiotic-associated gastrointestinal disturbances compared to the control group.
This study is expected to provide critical insights into the role of probiotic supplementation in mitigating antibiotic-induced dysbiosis, potentially shaping future guidelines for pediatric antibiotic therapy.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Varese, Italy
- Medicine & Technological Innovation Dept. University of Insubria
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Contact:
- Dr. Francesco Di Pierro, PhD
- Email: f.dipierro@vellejaresearch.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 3 to 12 years
- Requiring antibiotic therapy with Amoxicillin or Amoxicillin/Clavulanic Acid
- Ability to comply with the study protocol (parents/caregivers must complete symptom diaries)
Exclusion Criteria:
- Use of any antibiotic therapy within 3 months before study enrollment
- Known gastrointestinal diseases (e.g., inflammatory bowel disease, celiac disease)
- History of chronic diarrhea or constipation
- Allergy to probiotics or study interventions
- Any immunocompromised state
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Probiotic + Antibiotic Group (Probiotic Group)
Participants in this group will receive Amoxicillin or Amoxicillin/Clavulanic Acid as prescribed by their physician, and a probiotic as add-on for the duration of antibiotic therapy (6-10 days).
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Probiotic Bifidobacterium breve PRL2020 (Brevicillin®) at a dose of 20 billion CFU per day (one stick in the morning and one in the evening).
Other Names:
Treatment of Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.
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Active Comparator: Antibiotic-Only Group (Control Group)
Participants in this group will receive only Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.
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Treatment of Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Change in Antibiotic-Associated Gastrointestinal Symptoms
Time Frame: 15 days (treatment duration + follow-up)
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Evaluation of changes in gastrointestinal symptoms (diarrhea, bloating, abdominal pain, constipation) using the Bristol Stool Scale and a VAS symptom scale (0-7 points).
Participants will document symptoms in a daily symptom diary.
A significant reduction in symptoms in the probiotic group compared to the control group will indicate efficacy.
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15 days (treatment duration + follow-up)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Safety and Tolerability of Bifidobacterium breve PRL2020
Time Frame: 15 days
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Assessment of adverse events or intolerance to the probiotic supplementation.
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15 days
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Incidence of Antibiotic-Associated Diarrhea (AAD)
Time Frame: 15 days
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Proportion of participants developing diarrhea (≥3 loose stools/day for ≥2 days) as per WHO definition.
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15 days
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Changes in Stool Consistency and Frequency
Time Frame: 15 days
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Stool consistency will be assessed using the Bristol Stool Form Scale (BSFS), a validated 7-point scale where: Score 1 = Separate hard lumps (severe constipation), Score 7 = Watery, entirely liquid stools (severe diarrhea). Higher scores indicate looser stool consistency and a worse outcome in cases of diarrhea. Lower scores indicate constipation. Stool frequency will be recorded as the number of bowel movements per day. |
15 days
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Collaborators and Investigators
Collaborators
Publications and helpful links
General Publications
- Caron F, Ducrotte P, Lerebours E, Colin R, Humbert G, Denis P. Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings. Antimicrob Agents Chemother. 1991 Jun;35(6):1085-8. doi: 10.1128/AAC.35.6.1085.
- Mancabelli L, Mancino W, Lugli GA, Argentini C, Longhi G, Milani C, Viappiani A, Anzalone R, Bernasconi S, van Sinderen D, Ventura M, Turroni F. Amoxicillin-Clavulanic Acid Resistance in the Genus Bifidobacterium. Appl Environ Microbiol. 2021 Mar 11;87(7):e03137-20. doi: 10.1128/AEM.03137-20. Print 2021 Mar 11.
- Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334-9. doi: 10.1056/NEJMcp011603. No abstract available.
- Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O, Motola D, Dusi G, Caputi AP. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother. 2007 Jul;60(1):121-6. doi: 10.1093/jac/dkm111. Epub 2007 Apr 21.
- Yang L, Bajinka O, Jarju PO, Tan Y, Taal AM, Ozdemir G. The varying effects of antibiotics on gut microbiota. AMB Express. 2021 Aug 16;11(1):116. doi: 10.1186/s13568-021-01274-w.
- Di Pierro F, Campedelli I, De Marta P, Fracchetti F, Del Casale A, Cavecchia I, Matera M, Cazzaniga M, Bertuccioli A, Guasti L, Zerbinati N. Bifidobacterium breve PRL2020: Antibiotic-Resistant Profile and Genomic Detection of Antibiotic Resistance Determinants. Microorganisms. 2023 Jun 24;11(7):1649. doi: 10.3390/microorganisms11071649.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CESU/77/06.09.2023
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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