Probiotic-Antibiotic Combination for Recurrent Urinary Tract Infections

Overseen By Mehreen Arshad, MD

Age: < 18

Sex: Any

Trial Phase: Phase < 1

Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Must not be taking: Prophylactic antibiotics, Tizanidine

Disqualifiers: High-grade vesicoureteral reflux, Neurogenic bladder, Myasthenia gravis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with recurrent UTI were randomized to receive either the probiotic Sacchromyces Boulardii at enrollment, and the intracellularly active Ciprofloxacin with their first UTI episode after enrollment, or they received standard of care treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on prophylactic antibiotics or certain drugs that interact with ciprofloxacin. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Saccharomyces boulardii for recurrent urinary tract infections?

Saccharomyces boulardii has been shown to be effective in preventing and treating various types of diarrhea, including those associated with antibiotics, by improving gut health and supporting the immune system. While there is no direct evidence for its use in urinary tract infections, its ability to maintain a healthy balance of microorganisms in the body may offer some indirect benefits. ^{1 2 3 4 5}

Is the probiotic Saccharomyces boulardii safe for humans?

Saccharomyces boulardii is generally considered safe for use in children and adults, and is recommended in several international guidelines for managing acute diarrhea. However, there is a reported case of a serious infection (fungemia) in an elderly patient with a weakened condition, suggesting caution in such cases. ^{1 2 3 6 7}

What makes the treatment with Saccharomyces boulardii unique for recurrent urinary tract infections?

Saccharomyces boulardii is a unique probiotic yeast that can survive in a wide range of pH levels and does not acquire antibiotic resistance, making it different from bacterial probiotics. It is known for its ability to quickly stabilize in the gut and improve gut health, which may indirectly support the immune system and help prevent infections. ^{1 2 3 5 8}

Research Team

Mehreen Arshad

Principal Investigator

Lurie Children's Hospital

Eligibility Criteria

This trial is for children and teenagers aged 2-17 who have had at least three urinary tract infections (UTIs) in the past year or two in the last six months. They shouldn't have major bladder issues, any serious genitourinary surgery history, or be on antibiotics when joining.

Inclusion Criteria

I am not taking antibiotics to prevent infection.

I am between 2 and 17 years old.

I do not have, or only have mild, backward flow of urine from my bladder.

Exclusion Criteria

I have been diagnosed with myasthenia gravis.

I am under 2 years old.

I have had surgery on my urinary or digestive system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 250 mg of the probiotic Saccharomyces boulardii daily for 6 months. If symptoms of a UTI occur, they take 20 mg/kg of ciprofloxacin every 12 hours for 14 days.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Saccharomyces Boulardii

Trial Overview The study tests a new approach using the probiotic Saccharomyces Boulardii with Ciprofloxacin antibiotic at the first sign of UTI after enrollment versus standard care. Participants are randomly assigned to one of these treatments.

Participant Groups

Group I: Probiotic with or without antibiotic Experimental Treatment 1 Intervention

All patients will receive probiotics for this, only those with a UTI will get ciprofloxacin.

Group II: Control Active Control 1 Intervention

Patients will get standard of care treatment.

Saccharomyces Boulardii is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Saccharomyces Boulardii for:

• Prevention of antibiotic-associated diarrhea
• Prevention of Clostridioides difficile infection
• Supportive treatment for Helicobacter pylori infection

Approved in United States as Saccharomyces Boulardii for:

• Dietary supplement for gastrointestinal health
• Prevention of antibiotic-associated diarrhea
• Prevention of Clostridioides difficile infection

Approved in Canada as Saccharomyces Boulardii for:

• Prevention of antibiotic-associated diarrhea
• Prevention of Clostridioides difficile infection
• Supportive treatment for Helicobacter pylori infection

Who Is Running the Clinical Trial?

Ann & Robert H Lurie Children's Hospital of Chicago

Lead Sponsor

Trials

275

Recruited

5,182,000+

Findings from Research

Saccharomyces boulardii CNCM I-745 is an effective probiotic that significantly reduces the risk of antibiotic-associated diarrhea (AAD) and restores gut microbiota diversity, making it a valuable option for patients undergoing antibiotic treatment.

In children with pediatric acute gastroenteritis (PAGE), S. boulardii CNCM I-745 outperformed other probiotics, such as Lactobacillus rhamnosus GG, in reducing diarrhea duration and hospital stay, and is considered safe for both children and adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique Properties of Yeast Probiotic Saccharomyces boulardii CNCM I-745: A Narrative Review. Gopalan, S., Ganapathy, S., Mitra, M., et al.[2023]

Saccharomyces boulardii CNCM I-745 is a probiotic yeast that not only helps prevent and treat diarrhea but also enhances the expression of digestive enzymes and nutrient transport systems in the intestines, which is crucial for overall gut health.

The yeast works by secreting polyamines that promote cell growth and differentiation, and it activates important signaling pathways (like MAP kinase and PI3 kinase), contributing to its beneficial effects on the intestinal microbiota and nutrient absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Saccharomyces boulardii CNCM I-745 - the medicinal yeast improves intestinal enzyme function]. Moré, MI.[2019]

The probiotic Saccharomyces boulardii CNCM I-745 is effective in preventing and treating various types of diarrhea, including antibiotic-associated and Clostridium difficile-associated diarrhea, by enhancing the gut-associated immune system.

S. boulardii works through multiple mechanisms, including directly affecting pathogens and their toxins, modulating immune responses, and preserving the integrity of the intestinal lining, which helps reduce fluid leakage and inflammation during diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune system. Stier, H., Bischoff, SC.[2022]

Saccharomyces boulardii CNCM I-745 is a unique probiotic yeast that offers several mechanisms of action, including adhesion to harmful microorganisms, toxin elimination, and anti-inflammatory effects on the gut, making it effective in treating various gastrointestinal diseases.

This probiotic is particularly advantageous during antibiotic therapy because it is resistant to antibiotics, reducing the risk of promoting antimicrobial resistance, and is generally considered safe despite rare reports of fungemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Kaźmierczak-Siedlecka, K., Ruszkowski, J., Fic, M., et al.[2021]

The study confirmed the identity of Saccharomyces strains in 15 probiotic products as S. boulardii and introduced a rapid solid-phase cytometry (SPC) method for quantifying viable cells, which produced results significantly faster and with higher counts than traditional plating methods.

Less than 1% of S. boulardii cells survived in gastric conditions for 120 minutes, and their viability was greatly affected by storage conditions, highlighting the importance of gastric protection and proper storage for effective probiotic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality control of fifteen probiotic products containing Saccharomyces boulardii. Vanhee, LM., Goemé, F., Nelis, HJ., et al.[2018]

A case of fungemia (a yeast infection in the bloodstream) was reported in an elderly patient who was treated with the probiotic Saccharomyces boulardii alongside vancomycin for Clostridium difficile colitis.

The findings suggest that administering S. boulardii, especially in weakened patients with active colitis, may pose safety risks and is not recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces cerevisiae fungemia in an elderly patient with Clostridium difficile colitis. Cherifi, S., Robberecht, J., Miendje, Y.[2020]

In a study with BALB/c mice, feeding them Saccharomyces boulardii significantly increased total small intestinal immunoglobulin A levels by 1.8 times and specific anti-toxin A levels by 4.4 times after exposure to C. difficile toxoid A, indicating a strong immune response.

The findings suggest that the protective effects of S. boulardii against antibiotic-associated diarrhea and recurrent C. difficile colitis may be due to its ability to enhance the host's intestinal immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. Qamar, A., Aboudola, S., Warny, M., et al.[2018]

Saccharomyces boulardii CNCM I-745 is an effective probiotic for treating acute gastroenteritis, shown to safely reduce diarrhea duration and hospitalization by about one day, making it a recommended option for children by leading pediatric societies.

It is also beneficial in preventing antibiotic-associated diarrhea, improving treatment compliance and reducing side effects during Helicobacter pylori eradication, although there is insufficient evidence for its long-term use in irritable bowel syndrome and inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745 in different clinical conditions. Dinleyici, EC., Kara, A., Ozen, M., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Unique Properties of Yeast Probiotic Saccharomyces boulardii CNCM I-745: A Narrative Review. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[Saccharomyces boulardii CNCM I-745 - the medicinal yeast improves intestinal enzyme function]. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune system. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Quality control of fifteen probiotic products containing Saccharomyces boulardii. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Saccharomyces cerevisiae fungemia in an elderly patient with Clostridium difficile colitis. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745 in different clinical conditions. [2018]