Next Generation Sequencing for Urinary Tract Infections
Palo Alto (17 mi)Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Wake Forest University Health Sciences
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.
Is the drug Antibiotic a promising treatment for urinary tract infections?Yes, antibiotics are a promising treatment for urinary tract infections. They help fight the bacteria causing the infection. Advances in next-generation sequencing make it easier to identify the right antibiotic for each infection, improving treatment effectiveness.58101113
What safety data exists for next-generation sequencing in treating urinary tract infections?The provided research does not directly address the safety data for next-generation sequencing (NGS) in treating urinary tract infections. However, it discusses the safety and adverse reactions of various antibiotics used for UTIs, such as cinoxacin, which showed a 5% incidence of adverse drug reactions (ADRs) that were probably or definitely drug-induced. The studies highlight the importance of antimicrobial stewardship and the evaluation of newer antibiotics based on published reports and hospital antimicrobial sensitivity tests. While these studies provide insights into the safety of antibiotics, they do not specifically address NGS or PCR/NGS safety data.23459
What data supports the idea that Next Generation Sequencing for Urinary Tract Infections is an effective treatment?The available research does not provide specific data supporting the effectiveness of Next Generation Sequencing (NGS) for treating Urinary Tract Infections (UTIs). Instead, it focuses on traditional antibiotics and their effectiveness against UTIs. The research highlights the importance of using antibiotics that are effective against the specific bacteria causing the infection, especially in complicated cases. It also mentions the challenge of antibiotic resistance and the need for new antibiotics. However, there is no direct comparison or data on NGS as a treatment for UTIs in the provided information.156712
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications, but you cannot have taken antibiotics in the 2 weeks before joining the trial.
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.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Symptomatic Patients with low Colony CountExperimental Treatment2 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:
πΊπΈ Approved in United States as Antibiotics for:
- Bacterial infections
- Appendicitis
πͺπΊ Approved in European Union as Antibiotics for:
- Bacterial infections
- Appendicitis
π¨π¦ Approved in Canada as Antibiotics for:
- Bacterial infections
- Appendicitis
Find a clinic near you
Research locations nearbySelect from list below to view details:
Wake Forest Health SciencesWinston-Salem, NC
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Who is running the clinical trial?
Wake Forest University Health SciencesLead Sponsor
References
[Therapy of lower urinary tract infections in children]. [2006]Infection of the urinary tract has been described for nearly two centuries, yet the diagnosis, localization of infection, outcome, and management of UTI continue to generate significant problems. The two basic aims of treatment of UTI are the relief of symptoms and the prevention, or at least limitation, of damage to the renal parenchyma. The initial choice of an antimicrobial in the patient with a suspected UTI is based on knowledge of the expected organisms and their antimicrobial susceptibilities. The spectrum of urinary pathogens and their antibiotic susceptibility patterns in our geographical area are presented. Moreover therapeutic regimens in the treatment of upper and lower UTI are discussed.
The microbiological and pharmacokinetic profile of an antibacterial agent useful for the single-dose therapy of urinary tract infection. [2019]Single-dose therapy of uncomplicated urinary tract infection (UTI) has been shown to be effective in many trials in adult women. The question which will be explored in this presentation is what properties constitute the ideal agent for the therapy of UTI. Important microbiological properties include spectrum of activity to include all common urinary pathogens, bactericidal action in urine and low prevalence of resistant bacteria. The vital feature of an antibacterial drug useful in the therapy of UTI is prolonged urinary concentrations. The agent must therefore be well absorbed and have slow renal excretion. Most beta-lactam drugs do not have these combined properties. Aminoglycosides are effective drugs but cannot be administered orally. Quinolones and the calcium salt of fosfomycin are useful but do not have an ideal pharmacokinetic profile. Cotrimoxazole, trimethoprim alone and the trometamol salt of fosfomycin all have good antibacterial activity combined with slow urinary excretion.
Review of adverse reactions associated with cinoxacin and other drugs used to treat urinary tract infections. [2019]The evaluation of adverse drug reactions (ADR) in clinical practice is difficult and imprecise. Establishing a causal relationship may not be possible, and data on incidence cannot be obtained because the number of patients treated is not known. This article describes the ADR reported during the clinical trial program of cinoxacin, a synthetic antibacterial drug used to treat urinary tract infections. Results from 2,801 patients who received cinoxacin showed that 5 per cent reported ADR that were probably or definitely drug induced, and 10 per cent reported ADR in which the relationship was uncertain. There was no relationship between number of reports and patient's age, drug dose, or duration of treatment. Adverse drug reactions affecting the gastrointestinal system were reported by 5.5 per cent of the patients, those involving the central nervous system by 4.3 per cent, and hypersensitivity reported by 2.4 per cent. In the comparative studies, patients treated with cinoxacin reported fewer ADR than those treated with nalidixic acid, furadantin, amoxicillin, or trimethoprim-sulfamethoxazole. Although problems in the assessment and evaluation of ADR still exist, it is hoped that the results from the formal trial program will be representative of those seen in clinical practice.
Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. [2019]Cinoxacin, a chemotherapeutic agent that inhibits bacterial DNA synthesis, has recently been approved for the treatment of initial and recurrent bacterial urinary tract infections. Although closely related to nalidixic acid, cinoxacin possesses some distinct characteristics: rapid attainment of therapeutic urinary concentrations and greater activity against strains of Enterobacteriaceae that cause urinary tract infections. Biopharmaceutical properties include serum protein binding of approximately 70%, 50-60% excretion of intact drug in the urine of patients with normal renal function, and an elimination half-life of approximately one hour. The elimination half-life is increased in patients with decreased renal function and when probenecid is coadministered. Adverse events occur infrequently and consist of nausea, vomiting, headache, dizziness, and hypersensitivity reactions. The drug compares favorably with standard therapies for the treatment of bacterial cystitis and recurrent urinary tract infections. Initial studies demonstrate that cinoxacin has substantial efficacy as a prophylactic agent for those women who experience recurrent, symptomatic urinary tract infections.
Antimicrobial agents in urinary tract infections in patients with spinal cord injury. [2005]Because of the rapid introduction and active marketing of newer antimicrobial agents for urinary tract infections, it is important to evaluate newer antibiotics critically. Critical evaluation should be based on published reports, spectrum of action, and, very importantly, cost. Newer agents should be compared with known effective agents on the basis of hospital antimicrobial sensitivity tests. Simple, uncomplicated urinary tract infections caused by community-acquired multiple drug-sensitive uropathogens can be treated with almost any currently available antimicrobial agent. In these situations, a low-morbidity, low-cost agent with limited dosage should be chosen. In general, a 3-day course of trimethoprim-sulfamethoxazole, nitrofurantoin, a first-generation cephalosporin, a penicillin agent, or in some cases a fluoroquinolone will be both medically and cost effective. For complicated urinary tract infections, more selectivity must be exercised in choosing an appropriate antibacterial agent. In these situations, it is necessary to initiate appropriate diagnostic studies to identify causes and to treat those complications appropriately. The choice of antibiotics must be based on culture results. Initial empiric treatment should be carried out with a broad-spectrum agent of low morbidity. In these complicated infections, fluoroquinolones may be effective with low expected morbidity.
Emerging drugs for bacterial urinary tract infections. [2007]Bacterial urinary tract infections (UTIs) are frequent infections in the outpatient as well as in the nosocomial setting. The stratification into uncomplicated and complicated UTIs has proven to be clinically useful. Bacterial virulence factors on the one side and the integrity of the host defence mechanisms on the other side determine the course of the infection. In uncomplicated UTIs, Escherichia coli is the leading organism, whereas in complicated UTIs, the bacterial spectrum is much broader, including Gram-negative, Gram-positive and often multiresistant organisms. The therapy of uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated UTIs the complicating factors also have to be treated. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTIs: i) rapid and effective response to therapy and prevention of recurrence of the individual patient treated; and ii) prevention of emergence of resistance to chemotherapy in the microbial environment. The aim of this review is to highlight the existing, and to describe emerging, treatment options for UTIs.
Treatment of bacterial urinary tract infections: presence and future. [2022]Bacterial urinary tract infections (UTIs) are frequent infections in the outpatient as well as in the nosocomial setting. The stratification into uncomplicated and complicated UTIs has proven to be clinically useful. Bacterial virulence factors on the one side and the integrity of the host defense mechanisms on the other side determine the course of the infection. In uncomplicated UTIs Escherichia coli is the leading organism, whereas in complicated UTIs the bacterial spectrum is much broader including Gram-negative and Gram-positive and often multiresistant organisms. The therapy of uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated UTIs the complicating factors have to be treated as well. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTIs: (i) rapid and effective response to therapy and prevention of recurrence of the individual patient treated; (ii) prevention of emergence of resistance to antimicrobial chemotherapy in the microbial environment. The main drawback of current antibiotic therapies is the emergence and rapid increase of antibiotic resistance. To combat this development several strategies can be followed. Decrease the amount of antibiotics administered, optimal dosing, prevention of infection and development of new antibiotic substances. The aim of this review is to highlight the current and to describe future treatment options for UTIs.
Useful agents in the management of urinary tract infections. [2019]Urinary tract infections (UTIs) encompass a large variety of clinical conditions ranging from asymptomatic bacteriuria in healthy individuals to life-threatening bacteraemic infections. The choice of antibiotic therapy must be based on identification of the type of UTI to be treated, possible contraindicating factors with the individual patient and, above all, knowledge of the antibiotic resistance pattern in the geographical area where the patient acquired the bacteriuria. In many countries trimethoprim-sulphonamide combinations, trimethoprim plain or nitrofurantoin are still useful drugs. Generally, the clinical efficacy of oral beta-lactams such as amoxicillin, ampicillin and cephalosporins seems to be less good than those of fluoroquinolones and the above-mentioned antibiotics. However, too frequent use of quinolones may lead to increased frequencies of resistance to those antibiotics in common species such as Escherichia coli. It is therefore recommended not to used fluoroquinolones in patients with sporadic uncomplicated cystitis, i.e., the most common type of UTI, but to reserve the modern quinolones for patients with pyelonephritis, complicated UTI or recurrent UTI.
Novel Antibiotics in the Treatment of Urinary Tract Infections. [2019]Several new antibiotic agents for urinary tract infections include Ξ²-lactam/Ξ²-lactamase inhibitor combinations with cephalosporins and carbapenems. Siderophore cephalosporins, novel aminoglycosides, fluoroquinolones, and tetracyclines are also in clinical development. Nevertheless, antimicrobial stewardship remains important in preserving the utility of the antibiotic agents currently available.
Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review. [2023]Urinary tract infections, including cystitis, acute pyelonephritis, and prostatitis, are among the most common diagnoses prompting antibiotic prescribing. The rise in antimicrobial resistance over the past decades has led to the increasing challenge of urinary tract infections because of multidrug-resistant and "difficult-to-treat resistance" among Gram-negative bacteria. Recent advances in pharmacotherapy and medical microbiology are modernizing how these urinary tract infections are treated. Advances in pharmacotherapy have included not only the development and approval of novel antibiotics, such as ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, ceftolozane/tazobactam, cefiderocol, plazomicin, and glycylcyclines, but also the re-examination of the potential role of legacy antibiotics, including older aminoglycosides and tetracyclines. Recent advances in medical microbiology allow phenotypic and molecular mechanism of resistance testing, and thus antibiotic prescribing can be tailored to the mechanism of resistance in the infecting pathogen. Here, we provide a narrative review on the clinical and pre-clinical studies of drugs that can be used for difficult-to-treat resistant Gram-negative bacteria, with a particular focus on data relevant to the urinary tract. We also offer a pragmatic framework for antibiotic selection when encountering urinary tract infections due to difficult-to-treat resistant Gram-negative bacteria based on the organism and its mechanism of resistance.
Application of metagenomic next-generation sequencing in the diagnosis of urinary tract infection in patients undergoing cutaneous ureterostomy. [2023]Urinary tract infection (UTI) is an inflammatory response of the urothelium to bacterial invasion and is a common complication in patients with cutaneous ureterostomy (CU). For such patients, accurate and efficient identification of pathogens remains a challenge. The aim of this study included exploring utility of metagenomic next-generation sequencing (mNGS) in assisting microbiological diagnosis of UTI among patients undergoing CU, identifying promising cytokine or microorganism biomarkers, revealing microbiome diversity change and compare virulence factors (VFs) and antibiotic resistance genes (ARGs) after infection.
[Urinary tract infections including pyelonephritis]. [2023]Urinary tract infections (UTIs) are among the most common bacterial infections. The clinical phenotypes of UTIs are heterogeneous, ranging from rather benign uncomplicated infections to complicated UTIs and pyelonephritis to severe urosepsis. There has been a sharp increase in the incidence of severe UTIs, whilst the incidence of sepsis in general is declining. The classifications of UTIs partially differ between clinical and regulatory claims. Experience has also been gained over the last few years to define the appropriate endpoints that are used in clinical studies. Above all, patient-centered evaluation strategies of the endpoints were developed, in order to be able to identify the advantages of new antibiotics compared to traditional antibiotics. The development of new antibiotics for UTIs is essential, since multidrug-resistant enterobacteria, which belong to the typical bacterial spectrum of UTIs, are frequently associated with mortality from infections. In recent years, several new antibiotics/combinations that are particularly effective against multi-resistant gram-negative pathogens have been investigated for the treatment of UTIs.
Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model. [2023]Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens.