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Randomized Controlled Trial
. 2025 Mar 3;8(3):e250669.
doi: 10.1001/jamanetworkopen.2025.0669.

Probiotics and Fever Duration in Children With Upper Respiratory Tract Infections: A Randomized Clinical Trial

Silvia Bettocchi  1 , Anna Comotti  2 , Marina Elli  3 , Valentina De Cosmi  4   5 , Cristiana Berti  1 , Ilaria Alberti  1 , Alessandra Mazzocchi  5 , Chiara Rosazza  1 , Carlo Agostoni  1   5 , Gregorio Paolo Milani  1   5
Affiliations
Randomized Controlled Trial

Probiotics and Fever Duration in Children With Upper Respiratory Tract Infections: A Randomized Clinical Trial

Silvia Bettocchi et al. JAMA Netw Open. .

Erratum in

Abstract

Importance: Upper respiratory tract infections (URTIs) are prevalent in children, prompting frequent health care consultations, especially among those with fever. Probiotics show potential as an adjuvant treatment for URTIs, but evidence in children is limited.

Objective: To evaluate the efficacy of a probiotic mixture containing Bifidobacterium breve M-16V, Bifidobacterium lactis HN019, and Lactobacillus rhamnosus HN001 in shortening fever duration among children with URTIs.

Design, setting, and participants: This randomized clinical trial was conducted between November 19, 2021, and June 20, 2023, at the pediatric emergency department of the Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy. Patients between 28 days and 4 years of age with a fever (≥38.5 °C) and URTI were eligible. Exclusion criteria included recent probiotic use, chronic autoimmune diseases, immunosuppressive treatment, and requirement for hospitalization. Randomization was computer generated and assigned participants to either the intervention (probiotics) or control (placebo) group. Participants, parents or caregivers, and investigators were masked to the group assignments. The primary analysis followed the intention-to-treat approach.

Interventions: The probiotic group received daily single dose of 0.5 mL probiotic mixture containing Bifidobacterium breve M-16V, Bifidobacterium lactis HN019, and Lactobacillus rhamnosus HN001 for 14 days. The placebo group received daily single dose of 0.5 mL placebo for 14 days.

Main outcomes and measures: The primary outcome was fever duration, defined as the number of days between the first and the last days with fever.

Results: Of the 128 patients enrolled (69 males [54%]; mean [SD] age 2.5 [1.3] years), 65 (51%) were randomly assigned to receive placebo and 63 (49%) to receive probiotics. The median (IQR) fever duration was shorter in the probiotic group than the placebo group (median [IQR], 3 [2-4] days vs 5 [4-6] days; adjusted risk ratio, 0.64; 95% CI, 0.51-0.80). Few mild adverse events were reported and did not significantly differ between the probiotic and placebo groups, including constipation (6 [16%] and 6 [12%]; P = .80) and abdominal pain (3 [8%] and 2 [4%]; P = .65).

Conclusions and relevance: In this randomized clinical trial, administering a probiotic mixture reduced fever duration by 2 days compared with placebo, with no meaningful safety concerns. The probiotic mixture under investigation could be an effective adjuvant for shortening fever duration in children with URTIs.

Trial registration: ClinicalTrials.gov Identifier: NCT06052540.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Elli reported being employed by Coree Srl before and during part of the study. Prof Agostoni reported receiving consulting fees from Coree Srl outside the submitted work. Dr Milani reported receiving grants from Angelini Pharma SPA, personal fees from Angelini Pharma SPA, and grants from Reckitt Benckiser Healthcare SPA outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Participant Flow Diagram
See this image and copyright information in PMC

References

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