Next Generation Sequencing for Urinary Tract Infections

Overseen By Majid Mirzazadeh, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must not be taking: Antibiotics

Disqualifiers: Catheter use, Pregnancy, Incarceration, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect urinary tract infections (UTIs) using advanced techniques like Next Generation Sequencing (NGS). These methods can identify bacteria more accurately than traditional tests, especially in individuals with a low but present bacterial count. The trial tests whether these techniques help determine the appropriate antibiotic treatment for women with UTI symptoms and a low bacterial count in their urine. Women who have experienced UTI symptoms, tested positive with a low bacterial count, and have not taken antibiotics in the last two weeks are ideal candidates for this study. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for the trial?

The trial requires that you have not taken antibiotics in the past 2 weeks before signing the consent. Other medications are not mentioned, so it's best to discuss with the trial team.

What is the safety track record for these treatments?

Research has shown that next-generation sequencing (NGS) is a promising method for identifying bacteria in urine samples. Other studies have safely used it to help diagnose urinary tract infections (UTIs). This method examines the genetic material of bacteria to provide more accurate results than traditional methods.

The antibiotics in this trial are common medications often prescribed for UTIs. Most people tolerate antibiotics well, though some might experience mild side effects like an upset stomach or diarrhea. Since this trial is in a late phase, earlier studies have thoroughly tested the antibiotics, confirming their safety for treating UTIs.

In summary, both the NGS method and the antibiotics used in this trial have demonstrated safety for people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this trial?

Researchers are excited about using Next Generation Sequencing (NGS) for urinary tract infections (UTIs) because it offers a cutting-edge approach to identifying the specific bacteria causing an infection. Unlike traditional methods that rely on culturing to determine the presence of bacteria, which can sometimes be slow or miss low colony counts, NGS can quickly and accurately identify the specific pathogens present, even in cases with low bacterial counts. This precision allows for a more targeted use of antibiotics, potentially improving treatment outcomes and minimizing the risk of antibiotic resistance.

What evidence suggests that Next Generation Sequencing is effective for detecting bacteria in urinary tract infections?

Research has shown that Next Generation Sequencing (NGS), which participants in this trial may receive, effectively diagnoses urinary tract infections (UTIs). One study found that NGS correctly identified 90% of actual UTI cases. Another study demonstrated that NGS excels at detecting infections caused by multiple types of bacteria. This capability is crucial for patients with low bacterial levels, where traditional methods might miss the infection. Overall, NGS offers a promising tool for more accurately identifying and treating UTIs. ^{6 7 8 9 10}

Who Is on the Research Team?

Majid Mirzazadeh, MD

Principal Investigator

Wake Forest Health Sciences

Are You a Good Fit for This Trial?

This trial is for women aged 18 to 80 with a urinary tract infection (UTI) that's hard to detect using standard tests. They must be able to consent, follow the study schedule, and have low levels of bacteria in their urine. It's not for those who use catheters, can't give a clean urine sample, are pregnant or trying to conceive, incarcerated, or took antibiotics recently.

Inclusion Criteria

I am a woman aged between 18 and 80.

Able to give informed consent

You have a low amount of bacteria in your urine.

Exclusion Criteria

I have not taken antibiotics in the last 2 weeks.

You have a catheter in place.

You cannot provide a clean sample of urine collected midstream.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment based on Next Generation Sequencing results for UTI with low colony count

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment using King's Questionnaire Outcome

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antibiotic
• Next Gen

Trial Overview The trial is testing how well advanced DNA techniques like PCR and Next Generation Sequencing can identify UTI-causing bacteria compared to traditional methods. These new tests could be more sensitive for detecting low-level infections in patients.

How Is the Trial Designed?

Group I: Symptomatic Patients with low Colony Count Experimental Treatment 2 Interventions

Patients with positive urinalysis, symptomatic, and Urine Culture Colony Count \<10,000 to be treated based on Next Generation Sequencing result.

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

Approved in United States as Antibiotics for:

• Bacterial infections
• Appendicitis

Approved in European Union as Antibiotics for:

• Bacterial infections
• Appendicitis

Approved in Canada as Antibiotics for:

• Bacterial infections
• Appendicitis

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

The primary goals in treating urinary tract infections (UTIs) are to relieve symptoms and prevent kidney damage, highlighting the importance of timely and effective management.

Choosing the right antibiotic for a suspected UTI relies on understanding the common pathogens and their resistance patterns in the local area, which is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of lower urinary tract infections in children]. Principi, N., Viganò, A., Dalla Villa, A., et al.[2006]

Antimicrobial resistance is a significant challenge in treating urinary tract infections (UTIs), particularly for infections caused by Gram-negative bacteria that are resistant to common treatments like trimethoprim-sulfamethoxazole and fluoroquinolones.

There is a need for better diagnostic methods and the development of new antibiotics to effectively manage drug-resistant UTIs, as well as guidelines to avoid unnecessary treatment of asymptomatic cases and to use narrower-spectrum antibiotics when possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary tract infections. Drekonja, DM., Johnson, JR.[2018]

Escherichia coli is the primary cause of uncomplicated urinary tract infections (UTIs), while complicated UTIs involve a wider range of bacteria, including multiresistant strains, necessitating more complex treatment strategies.

Current antibiotic therapies face challenges due to rising antibiotic resistance, prompting the need for strategies such as optimizing dosing, reducing antibiotic use, and developing new treatments to effectively manage UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of bacterial urinary tract infections: presence and future. Wagenlehner, FM., Naber, KG.[2022]

A clinical trial involving 240 patients undergoing urologic stone interventions showed that next-generation sequencing (NGS) for microbial profiling significantly reduced the risk of postoperative urinary infections by 7.1% compared to standard care, indicating its efficacy in guiding antibiotic prophylaxis.

The study found that using NGS-guided antibiotic selection improved the match between prescribed antibiotics and actual urinary pathogens, which is crucial since mismatched antibiotics were linked to a higher risk of infection, particularly in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model. Liss, MA., Reveles, KR., Tipton, CD., et al.[2023]

The rise of antimicrobial resistance has made treating urinary tract infections (UTIs) more challenging, particularly with multidrug-resistant Gram-negative bacteria, prompting the need for new treatment strategies.

Recent advancements in pharmacotherapy have introduced novel antibiotics and revived older ones, while advances in medical microbiology enable tailored antibiotic prescribing based on the specific resistance mechanisms of the pathogens involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review. Chou, A., Welch, E., Hunter, A., et al.[2023]

Cinoxacin is an effective new treatment for initial and recurrent bacterial urinary tract infections, showing rapid therapeutic concentrations in urine and greater activity against certain bacteria compared to similar drugs.

The drug has a favorable safety profile with infrequent adverse events, and initial studies suggest it may also be beneficial as a preventive treatment for women prone to recurrent urinary tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. Scavone, JM., Gleckman, RA., Fraser, DG.[2019]

Escherichia coli is the primary cause of uncomplicated urinary tract infections (UTIs), while complicated UTIs involve a wider range of bacteria, including resistant strains, highlighting the need for tailored treatment approaches.

Effective treatment of UTIs focuses on achieving rapid relief from symptoms and preventing future infections, while also addressing the risk of antibiotic resistance in the bacteria involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging drugs for bacterial urinary tract infections. Wagenlehner, FM., Weidner, W., Naber, KG.[2007]

In a clinical trial involving 2,801 patients treated with cinoxacin for urinary tract infections, 5% reported adverse drug reactions (ADRs) that were likely caused by the drug, while 10% had uncertain relationships to the drug.

Patients taking cinoxacin experienced fewer ADRs compared to those treated with other antibiotics like nalidixic acid and amoxicillin, suggesting that cinoxacin may have a better safety profile in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of adverse reactions associated with cinoxacin and other drugs used to treat urinary tract infections. Burt, RA.[2019]

Antibiotic treatment for urinary tract infections (UTIs) should be tailored based on the type of UTI, patient factors, and local antibiotic resistance patterns, with trimethoprim-sulphonamide combinations and nitrofurantoin remaining effective options in many regions.

Fluoroquinolones should be reserved for more complicated cases of UTIs, such as pyelonephritis or recurrent infections, to prevent the development of antibiotic resistance, particularly against common bacteria like Escherichia coli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Useful agents in the management of urinary tract infections. Ragnar Norrby, S.[2019]

New antibiotic agents for urinary tract infections, including β-lactam/β-lactamase inhibitor combinations and novel classes like siderophore cephalosporins and aminoglycosides, are currently in clinical development.

Despite the introduction of these new antibiotics, it is crucial to practice antimicrobial stewardship to ensure the effectiveness of existing antibiotics is preserved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Antibiotics in the Treatment of Urinary Tract Infections. Naber, KG., Wagenlehner, FME.[2019]

Single-dose therapy for uncomplicated urinary tract infections (UTIs) is effective in adult women, but the ideal treatment agent must have specific properties such as a broad spectrum of activity against common urinary pathogens and the ability to maintain prolonged concentrations in urine.

Cotrimoxazole, trimethoprim, and the trometamol salt of fosfomycin are highlighted as effective options due to their good antibacterial activity and slow renal excretion, making them suitable for UTI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The microbiological and pharmacokinetic profile of an antibacterial agent useful for the single-dose therapy of urinary tract infection. Slack, R., Greenwood, D.[2019]

For simple urinary tract infections caused by drug-sensitive bacteria, low-cost antibiotics like trimethoprim-sulfamethoxazole or nitrofurantoin are effective and should be preferred due to their low morbidity and cost.

In cases of complicated urinary tract infections, it's crucial to perform diagnostic studies and base antibiotic choices on culture results, with broad-spectrum agents like fluoroquinolones being effective options with low expected morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial agents in urinary tract infections in patients with spinal cord injury. Carson, CC.[2005]

There has been a notable increase in severe urinary tract infections (UTIs), highlighting the need for new antibiotics, especially due to the rise of multidrug-resistant bacteria that can lead to serious complications like urosepsis.

Recent research has focused on developing patient-centered evaluation strategies for clinical studies, which aim to better assess the effectiveness of new antibiotics against traditional treatments for UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Urinary tract infections including pyelonephritis]. Wagenlehner, FME.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10996999/

Comparison of polymerase chain reaction and next- ... The study found that PCR has a 99% sensitivity and a 94% specificity for diagnosing UTIs. Furthermore, NGS was shown to have a sensitivity of 90% for ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0163445325000532

Rapid and accurate diagnosis of urinary tract infections ... Targeted Next Generation Sequencing (tNGS) demonstrated even greater efficiency in detecting polymicrobial infections, with co-occurrence patterns becoming ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10020507/

Enhancing urinary tract infection diagnosis for negative ... mNGS is a technology that has shown clear advantages over culture, particularly in the context of mixed infections and UTIs that are difficult ...

4. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09914-9

Exploring the clinical and diagnostic value of metagenomic ... The current evidence shows that mNGS has favorable diagnostic performance for UTIs. More high-quality prospective randomized controlled trials ( ...

5. urologytimes.com urologytimes.com/view/next-generation-sequencing-a-reliable-tool-for-the-diagnosis-and-treatment-of-complicated-and-recurrent-urinary-tract-infections

Next-generation sequencing: A reliable tool for the ... NGS through MicroGenDX eliminates the common equivocal result of “mixed urogenital flora” or “greater than 2 organisms predominate” encountered ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6935904/

Utility of DNA Next-Generation Sequencing and Expanded ... Improvement in symptom scores was significantly higher in those treated based on DNA testing, with an average 8.5-point improvement on the UTI ...

7. journals.asm.org journals.asm.org/doi/10.1128/jcm.00306-24

Novel technologies for the diagnosis of urinary tract infections This mini-review summarizes the existing state of UTI diagnostics in 2024 and covers current and upcoming technologies including rapid molecular-based pathogen ...

8. mdpi.com mdpi.com/2075-4418/15/19/2469

Emerging Technologies for the Diagnosis of Urinary Tract ... Next-generation sequencing (NGS), encompassing 16S ribosomal RNA gene sequencing, characterizes the urinary microbiome and frequently uncovers numerous ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07020676

NCT07020676 | Dynamics of the Urinary Bacterial Microbiota Evaluation of the abundance of different urotypes detected by the Next Generation Sequencing (NGS) technique in patients in the "UI" groups, At enrollment ...

10. frontiersin.org frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1221289/full

Advantage of precision metagenomics for urinary tract ... An implementation of next generation sequencing for prevention and diagnosis of urinary tract infection in urology. Can. J. Urol. 25 (3) ...