Urinary Tract Infections, Catheter-Related Infections
Conditions
Keywords
Urinary Tract Infections, Catheter-Related Infections, Pelvic Reconstructive Surgery, Urogynecology, Urinary catheterization, Post-operative Infections, Methenamine hippurate
Brief summary
The investigators will determine the efficacy of an innovative short regimen of methenamine hippurate on prevention of post-operative UTI in patients requiring short-term catheterization after pelvic reconstructive surgery through a single-blind, randomized controlled trial. Primary outcome will be the rate of symptomatic UTI within 3 weeks of catheter removal. The investigators will study cost-effectiveness, antibiotic resistance profiles, and adverse drug effects. Findings may reduce antibiotic use and nosocomial UTIs.
Detailed description
Prevention of post-operative urinary tract infections (UTI) is becoming important for both the individual patient and the health system. Complications of UTI include pyelonephritis and bacteremia, requiring hospitalization and parenteral antibiotics. Additionally, recurrent exposure to antibiotics commonly given for UTIs increases the risk of antibiotic resistance to uropathogens. UTIs also increase economic burdens on the health care system, with each episode costing nearly 600 dollars. UTIs associated with catheterization are particularly costly for hospitals, resulting in decreased hospital quality measures and lack of compensation. This is particularly important after pelvic reconstructive surgery, as reported rates of UTI reach up to 20-25%. Urinary retention requiring short-term indwelling catheterization, common in these women, contributes to the risk of UTIs by increasing the risk of bacteriuria by 5-10% per day and through the dislodging of bacterial colonies during catheter removal. Balancing prevention and resistance and cost is key. A meta-analysis by Marschall et al indicated the benefit of a short dose of antibiotic prophylaxis at catheter removal in general post-surgical patients. However, data is lacking on the effects of daily antibiotic prophylaxis on resistance and cost. A possible alternative to antibiotics presents itself in methenamine hippurate, a urinary antiseptic which forms formaldehyde in the presence of acidic urine. It is relatively inexpensive, and does not induce resistance in vivo. Prior studies have shown that daily use of methenamine can decrease the risk of post-operative UTI. The purpose of our study was to investigate the efficacy of a short course of methenamine hippurate at catheter removal to that of a short course of ciprofloxacin in prevention of UTIs after short-term indwelling catheterization. Additionally, we investigated factors that influence post-operative UTIs, the rate of culture-proven UTIs after prophylaxis, the antibiotic resistance profile of those undergoing prophylaxis, and the cost effectiveness of prophylaxis.
Interventions
A urinary antiseptic used for prevention of UTI
DRUGCiprofloxacin
An antibiotic used for treatment and prevention of UTI
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* female; * patients who are able to read and write English; * 18 years of age or older; * underwent surgery for pelvic organ prolapse, urinary incontinence, or both; * require post-operative short-term transurethral catheterization for greater than 24 hours.
Exclusion criteria
* patients undergoing surgical intervention for sacral neuromodulation, or mesh excision; * patients requiring long-term catheterization secondary to injury to the urinary tract; * patients who pass their post-operative trial void and thus, do not require additional catheterization; * patients requiring catheterization for less than 24 hours; * pregnant patients; * patients who are breast-feeding; * allergy to methenamine hippurate or fluroquinolones (either ciprofloxacin or levofloxacin); * impaired renal or hepatic function; * pre-operative urinary retention; * patients who are currently using sulfonamides; * patients who have severe dehydration; * patients using tizanidine; * patients sensitive to quinolones class; * patients using theophylline; patients with myasthenia gravis; * patients with prolongation of QT interval.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment of Clinically Suspected UTI - Per Protocol | 3 weeks post-operative | This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. |
| Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis | 3 weeks post-operative | This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibiotic Resistance of Culture-positive Symptomatic UTI | 3 weeks post-operative | All patients who submit urine cultures that are positive will have sensitivities performed as per standard care. The prevalence of bacterial species and sensitivities will be collected |
| Prevalence of Side Effects | within 24 hours of administration | Adverse effects from the administration of methenamine and fluoroquinolones will be collected. |
| Cost-effectiveness of Prophylaxis With Methenamine Hippurate for Prevention of Post-operative UTI Compared to Prophylaxis With Fluoroquinolones | 3 weeks post-operative | Routine costs of prevention of UTI with methenamine hippurate prophylaxis will be compared with costs of prevention of UTI with fluoroquinolone prophylaxis. We plan to capture costs for each direct medical service use, direct non-medical items, and indirect items related to post-operative UTIs in each arm of the trial. |
| Number of Participants With Culture-positive Symptomatic UTI | 3 weeks post-operative | All patients will be encouraged to submit urine cultures prior to treatment, but this is not always possible. Amongst patients who undergo urine culture as part of standard of care for UTI, the rate of positive cultures will be identified. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of UTI Consistent With NHSN Criteria | 3 weeks post-operative | We plan to analyze the prevalence of UTI in this population that meet the definitions of symptomatic UTI and catheter-associated UTI according to the National Healthcare Safety Network criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methenamine Methenamine hippurate is a medication that exhibits antibacterial activity by converting to formaldehyde in the presence of acidic urine. It is currently FDA approved for the prophylaxis of recurrent urinary tract infections. It has been previously used in studies for prevention of UTI after gynecologic surgery. Dosage will be methenamine hippurate 1g, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal.
methenamine hippurate: A urinary antiseptic used for prevention of UTI | 103 |
| Ciprofloxacin Ciprofloxacin is a commonly used antibiotic commonly used for prevention of UTI after catheterization. It belongs to a class of antibiotics known as the fluoroquinolones. Dosage will be ciprofloxacin 500 mg, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal.
Ciprofloxacin: An antibiotic used for treatment and prevention of UTI | 94 |
| Total | 197 |
Baseline characteristics
| Characteristic | Total | Ciprofloxacin | Methenamine |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10.6 | 61.6 years STANDARD_DEVIATION 10.5 | 63.9 years STANDARD_DEVIATION 10.7 |
| BMI | 27.6 kg/m^2 STANDARD_DEVIATION 5.1 | 28 kg/m^2 STANDARD_DEVIATION 5.3 | 27.1 kg/m^2 STANDARD_DEVIATION 4.9 |
| Current Smoker | 8 Participants | 5 Participants | 3 Participants |
| History of recurrent UTI | 8 Participants | 4 Participants | 4 Participants |
| Postmenopausal | 154 Participants | 71 Participants | 83 Participants |
| Race/Ethnicity, Customized Asian American/Pacific Islander | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 33 Participants | 18 Participants | 15 Participants |
| Race/Ethnicity, Customized Caucasion | 155 Participants | 72 Participants | 83 Participants |
| Race/Ethnicity, Customized Did not answer | 3 Participants | 2 Participants | 1 Participants |
| Recent preoperative UTI | 6 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 197 Participants | 94 Participants | 103 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 94 |
| other Total, other adverse events | 0 / 103 | 3 / 94 |
| serious Total, serious adverse events | 0 / 103 | 0 / 94 |
Outcome results
Primary
Treatment of Clinically Suspected UTI - Per Protocol
This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills.
Time frame: 3 weeks post-operative
Population: Per protocol model
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine | Treatment of Clinically Suspected UTI - Per Protocol | 12 Participants |
| Ciprofloxacin | Treatment of Clinically Suspected UTI - Per Protocol | 12 Participants |
Primary
Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis
This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills.
Time frame: 3 weeks post-operative
Population: Intent to Treat model
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine | Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis | 13 Participants |
| Ciprofloxacin | Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis | 12 Participants |
Secondary
Antibiotic Resistance of Culture-positive Symptomatic UTI
All patients who submit urine cultures that are positive will have sensitivities performed as per standard care. The prevalence of bacterial species and sensitivities will be collected
Time frame: 3 weeks post-operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine | Antibiotic Resistance of Culture-positive Symptomatic UTI | 0 Participants |
| Ciprofloxacin | Antibiotic Resistance of Culture-positive Symptomatic UTI | 0 Participants |
Secondary
Cost-effectiveness of Prophylaxis With Methenamine Hippurate for Prevention of Post-operative UTI Compared to Prophylaxis With Fluoroquinolones
Routine costs of prevention of UTI with methenamine hippurate prophylaxis will be compared with costs of prevention of UTI with fluoroquinolone prophylaxis. We plan to capture costs for each direct medical service use, direct non-medical items, and indirect items related to post-operative UTIs in each arm of the trial.
Time frame: 3 weeks post-operative
Population: The data for this secondary was not collected. No costs were captured.
Secondary
Number of Participants With Culture-positive Symptomatic UTI
All patients will be encouraged to submit urine cultures prior to treatment, but this is not always possible. Amongst patients who undergo urine culture as part of standard of care for UTI, the rate of positive cultures will be identified.
Time frame: 3 weeks post-operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine | Number of Participants With Culture-positive Symptomatic UTI | 5 Participants |
| Ciprofloxacin | Number of Participants With Culture-positive Symptomatic UTI | 4 Participants |
Secondary
Prevalence of Side Effects
Adverse effects from the administration of methenamine and fluoroquinolones will be collected.
Time frame: within 24 hours of administration
Population: The data for this secondary outcome measure was not collected.
Other Pre-specified
Rate of UTI Consistent With NHSN Criteria
We plan to analyze the prevalence of UTI in this population that meet the definitions of symptomatic UTI and catheter-associated UTI according to the National Healthcare Safety Network criteria.
Time frame: 3 weeks post-operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine | Rate of UTI Consistent With NHSN Criteria | 10 Participants |
| Ciprofloxacin | Rate of UTI Consistent With NHSN Criteria | 6 Participants |