Clinical trial NCT06850714: Evaluation of Bifidobacterium Breve PRL2020 in Preventing Antibiotic-Associated Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid
Official title: 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 type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Antibiotic Side Effect
Lead sponsor: Liaquat University of Medical & Health Sciences
Sponsor class: OTHER
Collaborators: name: Università degli Studi dell'Insubria
First posted: 2025-02-27
Enrollment: 800
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in Antibiotic-Associated Gastrointestinal Symptoms
timeFrame: 15 days (treatment duration + follow-up)
Secondary outcomes:
measure: Safety and Tolerability of Bifidobacterium breve PRL2020
timeFrame: 15 days
measure: Incidence of Antibiotic-Associated Diarrhea (AAD)
timeFrame: 15 days
measure: Changes in Stool Consistency and Frequency
timeFrame: 15 days
Other outcomes:
Locations:
city: Varese
country: Italy
facility: Medicine & Technological Innovation Dept. University of Insubria
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.