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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat recurring urinary tract infections (UTIs) by combining the probiotic Saccharomyces Boulardii with the antibiotic Ciprofloxacin. The researchers aim to determine if this combination is more effective than the usual treatment. One group of participants will receive the probiotic and, if a UTI occurs during the trial, the antibiotic; another group will receive standard care. This trial suits children and teens aged 2-17 who have experienced multiple UTIs in the past year but do not have serious bladder or urinary tract issues. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Saccharomyces boulardii is generally well-tolerated. Some research suggests it can help reduce symptoms in conditions like ulcerative colitis. However, rare reports exist of yeast infections in the bloodstream, even in individuals with healthy immune systems. While uncommon, this is important to mention.

Ciprofloxacin, a commonly used antibiotic for urinary tract infections (UTIs), is generally considered safe. Like all antibiotics, it can sometimes cause side effects, such as an upset stomach, dizziness, or, more rarely, serious tendon damage.

The combination of these treatments remains under study. As this trial is in its early phase, researchers focus primarily on safety, closely monitoring any issues. Participants will undergo screening to minimize risks, and the study team can address any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for UTIs?

Researchers are excited about this treatment because it combines probiotics with antibiotics in a novel way. While standard treatments for recurrent urinary tract infections (UTIs) typically rely on antibiotics alone, this approach uses Saccharomyces boulardii, a probiotic, to potentially enhance the gut microbiome and reduce antibiotic resistance. By introducing beneficial bacteria alongside antibiotics like ciprofloxacin, the treatment aims to not only combat infections more effectively but also support overall urinary and gut health. This dual-action strategy offers a promising alternative to traditional antibiotic therapy, which often struggles with resistance issues and recurring infections.

What evidence suggests that this probiotic-antibiotic combination might be an effective treatment for recurrent UTIs?

Research has shown that Saccharomyces boulardii, a type of probiotic, might help reduce urinary tract infections (UTIs). One study found that, when combined with D-Mannose, Saccharomyces boulardii significantly lowered the number of UTIs following a procedure called cystoscopy. Another study demonstrated that Saccharomyces boulardii can inhibit the growth of E. coli, a common bacteria causing UTIs. Additionally, Saccharomyces boulardii has effectively prevented diarrhea caused by antibiotics, suggesting it can maintain gut health. In this trial, participants in the experimental arm will receive Saccharomyces boulardii, and if a UTI occurs, they may also receive the antibiotic ciprofloxacin. These findings suggest that this combination could help reduce UTIs. ^{1 2 3 5 6}

Who Is on the Research Team?

Mehreen Arshad

Principal Investigator

Lurie Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10304042/

D-Mannose Plus Saccharomyces boulardii to Prevent ... Conclusions: D-Mannose plus Saccharomyces boulardii administered after cystoscopy seem to significantly reduce the incidence of UTI, the ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0732889316304096

Saccharomyces boulardii probiotic-associated fungemia We report a case of fungemia in an immunocompetent patient after administration of probiotic containing Saccharomyces boulardii.

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06149676/a-novel-probiotic-antibiotic-combination-to-prevent-recurrent-urinary-tract-infections

A Novel Probiotic-antibiotic Combination to Prevent ... Patients with recurrent UTI were randomized to receive either the probiotic Sacchromyces Boulardii at enrollment, and the intracellularly active ...

4. researchgate.net researchgate.net/publication/303162306_Inhibition_activity_of_Saccharomyces_boulardii_and_Lactobacillus_acidophilus_against_pathogenic_Ecoli_isolates_from_Recurrent_Urinary_Tract_Infection_in_women_In_Vitro

(PDF) Inhibition activity of Saccharomyces boulardii and ... The aims of study is to detect the inhibitory effect of Saccharomyces boulardii and Lactobacillus acidophilus on Escherichia coli that has been ...

5. withpower.com withpower.com/trial/early-phase-1-recurrence-1-2022-10388

Probiotic-Antibiotic Combination for Recurrent Urinary ... Saccharomyces boulardii has been shown to be effective in preventing and treating various types of diarrhea, including those associated with antibiotics, by ...

6. rxlist.com rxlist.com/supplements/saccharomyces_boulardii.htm

Saccharomyces Boulardii: Health Benefits, Side Effects, ... Early research shows that adding Saccharomyces boulardii to standard mesalamine therapy can reduce symptoms in people with mild-to-moderate ulcerative colitis.