Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children: A Randomized Clinical Trial
Jan Lukasik1, Thomas Dierikx2, Isolde Besseling-van der Vaart3
1Department of Pediatrics, The Medical University of Warsaw, Warsaw, Poland.
Insights
A multispecies probiotic did not prevent antibiotic-associated diarrhea (AAD) in children but reduced the overall risk of diarrhea during and after antibiotic treatment. Study highlights the impact of AAD definitions on trial outcomes.
Area of Science:
- Microbiology
- Clinical Trials
- Gastroenterology
Background:
- Antibiotic-associated diarrhea (AAD) is a common concern, particularly in children.
- The efficacy of multispecies probiotics in preventing AAD is not well-established.
- Understanding the impact of probiotic interventions is crucial for clinical practice.
Purpose of the Study:
- To evaluate the effect of a specific multispecies probiotic formulation on the incidence of AAD in pediatric patients.
- To assess secondary outcomes including overall diarrhea risk, duration, and complications.
- To analyze the influence of diagnostic criteria on AAD prevention trial results.
Main Methods:
- A randomized, quadruple-blind, placebo-controlled trial involving 350 children aged 3 months to 18 years.
- Participants received a daily dose of a multispecies probiotic or placebo during and for 7 days after antibiotic therapy.
- Primary outcome was AAD; secondary outcomes included diarrhea regardless of etiology and complications.
Main Results:
- The multispecies probiotic did not significantly reduce the risk of AAD compared to placebo (RR, 0.81; 95% CI, 0.49-1.33).
- However, the probiotic group showed a significantly lower risk of diarrhea of any cause (RR, 0.65; 95% CI, 0.44-0.94).
- No significant differences were found in adverse events or most secondary outcomes.
Conclusions:
- Multispecies probiotics, under the stringent AAD definition used, did not prevent AAD in children.
- The formulation demonstrated a benefit in reducing the overall incidence of diarrhea during and post-antibiotic treatment.
- The definition of AAD significantly impacts clinical trial outcomes and their interpretation.
Importance:
The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear.
Objective:
To assess the effect of a multispecies probiotic on the risk of AAD in children.
Design, Setting, And Participants:
This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial.
Interventions:
A multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after.
Main Outcomes And Measures:
The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications.
Results:
A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events.
Conclusions And Relevance:
A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03334604.
More Related Videos
Related Concept Videos
01:18Drugs Affecting GI Tract Motility: Antimicrobials as Antidiarrheal Agents
01:17Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
01:20Drugs Affecting GI Tract Motility: Adsorbents as Antidiarrheal Agents
Adsorbents...
00:57Antibiotic Selection
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...