Single Dose Aminoglycosides for Acute Uncomplicated Cystitis in the Emergency Department Setting

January 18, 2023 updated by: Mercy Health Ohio
The purpose of this research study is to determine if gentamicin is as effective treatment of acute uncomplicated cystitis (urinary tract infection) using aminoglycosides versus the current standards of care. The current standards of care in our region are often to prescribe a multi-day antibiotic prescription that is taken multiple times per day whereas gentamicin will be a one-time dose in the emergency department. Gentamicin is the medicine being studied.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Urinary tract infections (UTIs) account for more than 8 million office visits and 1 million emergency department visits each year in the United States, making them one of the most often encountered indications for antibiotic use in ambulatory care. Escherichia Coli has been shown to be the main cause of uncomplicated cystitis, occurring in 75-95% of cases, with other Enterobacteriaceae like Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus comprising the majority of the other potential causes of cystitis. E. coli is also the most frequently encountered nitrite positive Enterobacteriaceae locally as well, representing nearly 3 out of every 4 culture specimens in the Boardman-specific gram-negative urine antibiogram (74%), 209 out of 284 to be exact. Some of the typical antibiotics used to treat these organisms had seen rising resistance rates from 2003-2012, with substantial increases in the resistance to both ciprofloxacin (3.6% to 11.8%) and trimethoprim-sulfamethoxazole (17.2% to 22.2%) in the United States. Gentamicin offers 93% sensitivity towards E. coli in the local antibiogram, whereas sulfamethoxazole-trimethoprim and fluoroquinolones offer 75% and 69%, respectively. More importantly, the current standard of care, cefdinir, only offers around 80% sensitivities locally. While nitrofurantoin has retained high levels of antibiotic activity against E. coli, it is contraindicated in the elderly and patients with poor renal function. This growing rate of resistance has placed a larger emphasis on finding alternative treatment options.

As stated above, Goodlet et al. reviewed 13 studies totaling 13,804 patients, and data from 11 out of the 13 revealed a microbiological cure rate of 94.5% +/- 4.3% using single dose aminoglycosides to treat urinary tract infections. Seven of these studies had comparator groups that included medications such as oral cephalosporins, Fosfomycin, trimethoprim-sulfamethoxazole and amoxicillin. No difference in initial or sustained microbiological cure rate in those that received aminoglycosides versus other medications was demonstrated. Only two of the thirteen studies evaluated clinical cure rates which were shown to be 82.8% and 94.7%, respectively. In the studies with 30 day follow up, an overall recurrence rate at 30 days was found to be 19% (84/443 patients). The recurrence rate seen using aminoglycosides is improved when compared to the general population, as 27% of women have been found to experience recurrence of their symptoms within 6 months of having urinary tract infections. Aminoglycosides were at one time a standard first-line therapeutic option to treat UTIs but fell out of favor due to their side effect profile.

The most concerning adverse effects of aminoglycosides were mainly seen in association with multi-day regimens of the drugs. Their nephrotoxic and ototoxic effect are seen in less than 1% of patients evaluated, but saw their use decrease roughly 41% between 2002-2009. In the Goodlet et al. study only 63 of the 13,804 patients (0.5%) reported adverse effects associated with the single dose aminoglycoside treatment. Only 7 total cases (0.05%) reported nephrotoxicity and 53 total cases (0.38%) reported signs of vestibular toxicity such as tinnitus and equilibrium disorders. Additionally, in a study of over 10,000 patients receiving single dose amikacin for UTI, nephrotoxicity was only reported in 0.04% of cases. Another review looking at 24,107 patients that had received a single dose of gentamicin reported no cases of ototoxicity as well. Comparably, sulfamethoxazole-trimethoprim carries common and rare risks of hyperkalemia, blood dyscrasias, hypersensitivity reactions, and other adverse events affecting nearly every organ system of the body. Fluoroquinolones carry common and rare risks of QT segment prolongation, peripheral neuropathy, dysglycemia, adverse events affecting the whole body and even a long-term syndrome effecting tens of thousands of people called fluoroquinolone-associated disability (FQAD). Beta-lactams such as cefdinir commonly cause gastrointestinal symptoms but more rarely effect other organ systems such as the skin, metabolic and hematologic abnormalities, and other adverse events as well. While adverse effects may occur with aminoglycosides, the studied risk of single dose use is not extreme and comparable with adverse effects seen with current standards of care.

While there is a proven cure rate utilizing single dose aminoglycosides to treat acute uncomplicated cystitis, they will also provide several other benefits when used in the emergency department setting. The single dosing of antibiotic in the emergency department removes the need for patient adherence to outpatient antibiotic therapy, thus reducing possible bounce back visits. Gentamicin can also be administered intramuscularly, as it was in all the above studies, both removing the need for IV access and expediting possible disposition in the emergency department. Lastly, greater than 75% of outpatient UTI prescriptions are written for durations that are not recommended, which is an issue that can be removed from the equation entirely utilizing single dose treatment. Treating patients with single dose aminoglycosides for acute uncomplicated cystitis in the emergency department may provide better compliance with the same efficacy, resulting in a new standard of care for treatment in the emergency department.

Study Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Youngstown, Ohio, United States, 44501
        • Recruiting
        • St. Elizabeth Youngstown Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • At least 18 years of age, woman, pre-menopausal, non-pregnant with clinical signs of urinary tract infection and nitrite positive urine.

Exclusion Criteria:

  • Contraindications include hypersensitivity to gentamicin or other aminoglycosides.
  • Patients younger than 18 years of age.
  • Pregnant or post-menopausal patients.
  • Patients without symptoms of UTI, nitrite negative urine, or any patient with working diagnosis of complicated UTI such as pyelonephritis or any patient catheterized.
  • ANY history of pre-existing renal impairment.
  • Patient that has any listed or reports taking ANY nephrotoxic or wit drug-drug interaction medication in the past 7 days (see Appendix 5).
  • ANY history of hearing loss, tinnitus, or vertigo.
  • ANY patient that has received general anesthesia or neuromuscular blockade in past 7 days.
  • Patients with ANY history of neuromuscular disorders including: myasthenia gravis, amyotrophic lateral sclerosis, muscular dystrophy, botulism, congenital myasthenic syndromes, congenital myopathies, myositis, Lambert-Eaton syndrome, mitochondrial myopathy, myotonic dystrophy, neuromyotonia, or peripheral neuropathy.
  • Patients with ANY history of thrombocytopenia.
  • Patient that has any listed or reports taking ANY anticoagulants in the past 7 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Gentamicin
Subjects will be given one (1) injection intramuscular gentamicin 5 mg/kg (actual body weight unless patient is >120% ideal body weight in which case adjusted body weight will be utilized).
Drug: Gentamicin
5 mg/kg intramuscular injection
Active Comparator: Standard of Care
Oral antibiotic prescription
Drug: Standard of Care
Usual oral antibiotic multi-day dosing based on local antibiogram
Other Names:
  • Oral dose regimen for simple urinary tract infection: Including cephalexin, cefdinir, sulfamethoxazole/trimethoprim, and nitrofurantoin at appropriate dose, frequency, and duration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Resolution
Time Frame: 7 days from presentation
If patient is or is not still having any pain with urination, urinary frequency or urinary urgency
7 days from presentation
Clinical Resolution
Time Frame: 30 days from presentation
If patient is or is not still having any pain with urination, urinary frequency or urinary urgency
30 days from presentation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mercy Health Ohio

Collaborators

Northeast Ohio Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2022

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

June 30, 2024

Study Registration Dates

First Submitted

September 22, 2022

First Submitted That Met QC Criteria

January 18, 2023

First Posted (Actual)

January 27, 2023

Study Record Updates

Last Update Posted (Actual)

January 27, 2023

Last Update Submitted That Met QC Criteria

January 18, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-010

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Urinary Tract Infections

Clinical Trials on Gentamicin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bangladesh

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe