Next Generation Sequencing for Urinary Tract Infections

Overseen by Majid Mirzazadeh, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Wake Forest University Health Sciences

Must not be taking: Antibiotics

Disqualifiers: Catheter use, Pregnancy, Incarceration, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Recently more advanced techniques, including Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) are available to detect bacteria in urine based on bacterial genomes. Comparing to traditional culture, these techniques have more sensitivity and could potentially be of a great help in patients with Colony Count of less than 10,000 and more than zero.

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 data supports the effectiveness of the treatment Next Generation Sequencing for Urinary Tract Infections?

The research highlights that new antibiotics, which are part of the treatment, are essential for treating UTIs, especially those caused by multidrug-resistant bacteria. Additionally, the use of broad-spectrum antibiotics, which are included in the treatment, is effective for complicated UTIs. ^{1 2 3 4 5}

Is Next Generation Sequencing for Urinary Tract Infections safe for humans?

The safety of antibiotics used for urinary tract infections has been studied, with some new antibiotics showing low rates of side effects like nausea and dizziness. In studies, cinoxacin, a type of antibiotic, had fewer side effects compared to other common treatments, suggesting that these treatments are generally safe for humans. ^{1 6 7 8 9}

How is the drug used in the clinical trial for urinary tract infections different from other treatments?

The drug in the clinical trial uses next-generation sequencing (NGS) to more accurately identify the bacteria causing the infection, allowing for a more targeted antibiotic choice. This approach is unique because it increases the sensitivity of detecting urinary pathogens, potentially leading to more effective treatment compared to traditional methods that may not account for specific bacterial resistance patterns. ^{1 10 11 12 13}

Research Team

Majid Mirzazadeh, MD

Principal Investigator

Wake Forest Health Sciences

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Antibiotic (Antibiotic)
• Next Gen (NGS Device)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. L. Ebony Boulware

Wake Forest University Health Sciences

Chief Medical Officer since 2022

MD from Duke University School of Medicine, MPH from Johns Hopkins Bloomberg School of Public Health

Dr. Julie Ann Freischlag

Wake Forest University Health Sciences

Chief Executive Officer since 2020

BS from University of Illinois, MD from Rush University

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of bacterial urinary tract infections: presence and future. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Urinary tract infections including pyelonephritis]. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Emerging drugs for bacterial urinary tract infections. [2007]

5. Italy pubmed.ncbi.nlm.nih.gov

[Therapy of lower urinary tract infections in children]. [2006]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Novel Antibiotics in the Treatment of Urinary Tract Infections. [2019]

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

Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. [2019]

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. Netherlands 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. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Useful agents in the management of urinary tract infections. [2019]

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

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

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

Urinary tract infections. [2018]