Evaluation of the Use of a Probiotic Containing Bifidobacterium Breve PRL2020 in Oral Drops in Preventing Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid Antibiotic Use

Evaluation of the Use of a Probiotic Containing Bifidobacterium Breve PRL2020 in Oral Drops in Preventing Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid Antibiotic Use: a Multicentre, Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial

This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of the probiotic Bifidobacterium breve PRL2020 (Brevicillin® gocce) in preventing gastrointestinal side effects associated with antibiotic therapy using amoxicillin or amoxicillin/clavulanic acid in pediatric patients aged 0-12 years. Participants will be randomized 1:1 to receive either the probiotic supplement or placebo during standard antibiotic treatment for 6-10 days, followed by a post-treatment observation period up to day 15 without probiotic or placebo administration. The primary objective is to assess the reduction in the incidence of antibiotic-associated diarrhea (AAD).

Study Overview

• Status: Not yet recruiting
• Conditions: Antibiotic-associated Diarrhea
• Intervention / Treatment: Dietary supplement: Brevicillin® gocce (Bifidobacterium breve PRL2020); Other: Placebo (matching oil drops)

Detailed Description

Antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid is widely prescribed in pediatric populations but is frequently associated with gastrointestinal adverse effects, particularly diarrhea. These effects are linked to disruption of the gut microbiota and a reduction in bifidobacterial populations. Bifidobacterium breve PRL2020 is a probiotic strain with demonstrated intrinsic, non-transferable resistance to these antibiotics and has been developed to mitigate antibiotic-induced dysbiosis.

This study is a multicenter, prospective, randomized, double-blind, placebo-controlled, non-profit trial conducted in pediatric centers across Italy. The study aims to evaluate the clinical efficacy and safety of Bifidobacterium breve PRL2020 in reducing the incidence and severity of antibiotic-associated diarrhea (AAD) in children receiving amoxicillin or amoxicillin/clavulanic acid.

A total of 1,000 participants (500 per group) will be enrolled. Participants will be randomized 1:1 to receive either Brevicillin® gocce (5 drops 2-3 times daily, containing 5 billion CFU of B. breve PRL2020 per dose) or matching placebo only during antibiotic therapy (6-10 days). After completion of antibiotic treatment, participants will enter a follow-up period until day 15 without probiotic or placebo administration.

The primary outcome is the incidence of AAD, defined as ≥3 diarrheal episodes in one day during antibiotic treatment (Bristol Stool Scale 5-7).

Secondary outcomes include the incidence and duration of diarrhea, daily bowel movements, stool consistency, gastrointestinal and extra-intestinal symptoms (such as nausea, vomiting, abdominal pain), treatment compliance, and adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Davide Sisti, PhD; Phone Number: +39-0722-303301; Email: davide.sisti@uniurb.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female participants aged 0-12 years.
• Undergoing antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid.
• Parent or legal guardian provides written informed consent.

Exclusion Criteria:

• Use of antibiotic therapy within 4 weeks prior to enrolment.
• Use of other probiotic products or lactic acid bacteria during the study.
• Pre-existing diarrhea within 4 weeks prior to enrolment.
• Chronic inflammatory bowel disease.
• Immunodeficiency.
• Lack of parental or legal guardian consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brevicillin® gocce (Bifidobacterium breve PRL2020); Participants will receive Brevicillin® gocce, a probiotic food supplement containing Bifidobacterium breve PRL2020 (LMG S-32458), alongside standard antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid. Dosage and administration: 5 drops, 2-3 times per day (depending on antibiotic dosing schedule), administered during the antibiotic treatment period (6-10 days). After completion of antibiotic therapy, participants will enter a follow-up period until day 15 without probiotic administration.	Dietary supplement: Brevicillin® gocce (Bifidobacterium breve PRL2020); Brevicillin® gocce is a probiotic dietary supplement in oily drops containing the bacterial strain Bifidobacterium breve PRL2020 (LMG S-32458). Each 5-drop dose contains approximately 5 billion live cells. The supplement is administered orally 2-3 times per day, in parallel with antibiotic therapy (amoxicillin or amoxicillin/clavulanic acid), for 6-10 days only (during the antibiotic course). After completion of antibiotic therapy, participants enter a follow-up period until day 15 without probiotic administration. The product is manufactured by PharmExtracta S.p.A., Pontenure, Italy.
Placebo Comparator: Placebo; Participants will receive a placebo formulation matched in appearance, packaging, and dosing schedule to Brevicillin® gocce, administered alongside standard antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid. The placebo will be given at the same frequency (5 drops, 2-3 times per day) and duration as the experimental product during the antibiotic treatment period (6-10 days). After antibiotic completion, participants will enter a follow-up period until day 15 without placebo administration.	Other: Placebo (matching oil drops); The placebo is a formulation identical in appearance, packaging, and administration schedule to Brevicillin® gocce but without the Bifidobacterium breve PRL2020 strain. It is administered orally 2-3 times per day only during the antibiotic treatment period (6-10 days). After antibiotic completion, participants enter a follow-up period until day 15 without placebo administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Antibiotic-Associated Diarrhea (AAD)	Evaluation of the efficacy of Bifidobacterium breve PRL2020 (Brevicillin® gocce) in reducing the incidence of antibiotic-associated diarrhea (AAD), defined as ≥3 diarrheal episodes within one day of antibiotic treatment, with stool consistency corresponding to types 5-7 on the Bristol Stool Scale. Data will be collected through a daily diary completed by the parent or legal guardian.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of children with at least one episode of diarrhea	Number of participants experiencing at least one episode of diarrhea during the study period, as recorded in the daily diary.	15 days
Number of daily defecations	Average number of daily bowel movements recorded by the parent or guardian during the study period, using the child's daily diary.	15 days
Number of days with diarrhea	Total number of days in which diarrhea occurs during the observation period, recorded by the parent or guardian.	15 days
Stool consistency	Assessment of stool consistency using the Bristol Stool Scale (BSS) to evaluate changes in bowel habits during and after antibiotic treatment.	15 days
Gastrointestinal and extra-intestinal symptoms	Evaluation of symptoms related to antibiotic use, including abdominal pain, nausea, and vomiting, assessed from daily diary entries completed by the parent or guardian	15 days
Treatment compliance	Assessment of adherence to the probiotic or placebo regimen, graded by the pediatrician on a scale from "poor" to "excellent" at the end of the study period.	15 days
Adverse events	Documentation and evaluation of any adverse events reported during treatment and follow-up, as recorded in the child's daily diary and verified by the study physician.	15 days

Collaborators and Investigators

• Sponsor: Liaquat University of Medical & Health Sciences
• Collaborators: University of Urbino "Carlo Bo"
• Investigators: Principal Investigator: Davide Sisti, PhD, University of Urbino "Carlo Bo"

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.
• Biasucci G, Capra ME, Giudice A, Monopoli D, Stanyevic B, Rotondo R, Mucci A, Neglia C, Campana B, Esposito S. Use of Probiotics During Antibiotic Therapy in Pediatrics: A Cross-Sectional Survey of Italian Primary Care Pediatricians. Antibiotics (Basel). 2025 Jun 4;14(6):577. doi: 10.3390/antibiotics14060577.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): May 29, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Estimated): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: Brevicillin_PRL2020_Trial

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