Evaluation of Bifidobacterium Breve PRL2020 in Preventing Antibiotic-Associated Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid

NCT ID: NCT06850714

Last Updated: 2025-03-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-23
• Study Completion Date: 2025-12-31

Brief Summary

This study aims to evaluate the efficacy and safety of the probiotic Bifidobacterium breve PRL2020 in preventing gastrointestinal and extra-intestinal side effects caused by Amoxicillin or Amoxicillin/Clavulanic Acid in pediatric patients. The study will compare a treatment group receiving the probiotic alongside antibiotics with a control group receiving antibiotics alone. The primary focus is on reducing antibiotic-induced intestinal discomfort through microbiota modulation.

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.

Conditions

Antibiotic Side Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Bifidobacterium breve PRL2020 (Brevicillin®)

Intervention Type: DIETARY_SUPPLEMENT

Probiotic Bifidobacterium breve PRL2020 (Brevicillin®) at a dose of 20 billion CFU per day (one stick in the morning and one in the evening).

Amoxicillin or Amoxicillin/Clavulanic Acid

Intervention Type: DRUG

Treatment of Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.

Antibiotic-Only Group (Control Group)

Participants in this group will receive only Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.

Group Type: ACTIVE_COMPARATOR

Amoxicillin or Amoxicillin/Clavulanic Acid

Intervention Type: DRUG

Treatment of Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.

Interventions

Bifidobacterium breve PRL2020 (Brevicillin®)

Probiotic Bifidobacterium breve PRL2020 (Brevicillin®) at a dose of 20 billion CFU per day (one stick in the morning and one in the evening).

Intervention Type: DIETARY_SUPPLEMENT

Amoxicillin or Amoxicillin/Clavulanic Acid

Treatment of Amoxicillin or Amoxicillin/Clavulanic Acid as per medical prescription.

Intervention Type: DRUG

Other Intervention Names

Brevicillin®, PharmExtracta S.p.A.

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università degli Studi dell'Insubria

OTHER

Sponsor Role: collaborator

Liaquat University of Medical & Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Dr. Amjad Khan

Professor of Clinical Biochemistry and Experimental medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medicine & Technological Innovation Dept. University of Insubria

Varese, , Italy

Countries

Italy

Facility Contacts

Dr. Francesco Di Pierro, PhD

Role: primary

f.dipierro@vellejaresearch.com

References

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.

Reference Type: BACKGROUND

PMID: 11821511 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17449881 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1929247 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34398323 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33483308 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37512822 (View on PubMed)

Other Identifiers

CESU/77/06.09.2023

Identifier Type: -

Identifier Source: org_study_id