Clinical trial NCT03099863
Conditions: Urinary Tract Infections
Sponsor: MetroHealth Medical Center
Start date: 2016-04-01; Completion date: 2020-06-01
Enrollment: 242 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Postoperative urinary tract infections (UTIs) affect 20-30% of patients undergoing elective gynecologic surgery and have a significant socioeconomic impact and cost. Preoperative antibiotics, sterile operating techniques, postoperative antibiotic and non-antibiotic medical therapies have been utilized to attempt to decrease this rate with little improvement. Utilization of an intraoperative antibiotic cystoscopic irrigant may decrease postoperative UTIs. The investigators have designed a prospective randomized controlled study to evaluate the effectiveness of an antibiotic cystoscopic fluid in preventing postoperative urinary tract infections in women undergoing elective pelvic floor surgery with cystoscopy.

Detailed description:

Arms: arm 1: Standard cystoscopy with normal saline solution. arm 2: Standard cystoscopy with normal saline solution containing Neosporin® G.U. at a 1mL/1000mL concentration.
Interventions: intervention 1: Cystoscopic Fluid containing Neosporin G. U. Irrigant intervention 2: Cystoscopy intervention 3: Cystoscopic Fluid/Placebo
Intervention descriptions: intervention 1: Normal saline cystoscopic fluid containing Neosporin G. U. Irrigant 1mL/1000mL intervention 2: Diagnostic cystoscopy performed during pelvic floor surgery intervention 3: Normal saline cystoscopic fluid

Protocol documents:
Prot_SAP_000.pdf: 
 
Cover Sheet 
 
Title: Cytoscopic Antibiotic Irrigant to Reduce Postoperative Urinary Tract Infection 
ID: IRB15-00769 
 
Document Date: November 30th, 2021 
 


Study Protocol and Statistical Analysis 
 
MATERIALS AND METHODS  
This was an investigator-initiated double-blind randomized controlled trial approved by the 
Institutional Review Board at MetroHealth Medical Center in Cleveland, OH and registered with 
clinicaltrials.gov (CT03099863). We conducted and reported this study according to the 
consolidated standards of reporting trials guidelines for randomized controlled trials.1 An 
independent data safety monitoring committee oversaw this trial. We had no extra-institutional 
funding.  
 
DESIGN, SETTING, AND PARTICIPANTS  
This study was performed between May 2016 and September 2019 at a single academic 
medical center. Adult women were eligible to participate if they were scheduled to undergo 
elective surgery by two female pelvic medicine and reconstructive surgery or minimally invasive 
gynecology surgery staff that would require intraoperative cystoscopy, including POP repair, 
mid- urethral sling placement (MUS), hysterectomy, and complicated excision of endometriosis. 
Cystoscopy is routinely performed with these procedures in our practice. Exclusion criteria 
included history of neurogenic bladder, recurrent UTIs, nephrolithiasis, congenital urogenital 
anomaly, allergy to neomycin or polymyxin, pregnancy, or surgery planned to include 
intradetrusor onabotulinumtoxin A injection, mesh excision, or fistula repair. Women were 
excluded if they were found to have a positive urine culture on routine preoperative testing, 
independent of symptoms, or from an intraoperative urine sample. All subjects provided 
written informed consent. Participation in this study did not have any direct benefit to 
individual subjects.  
 
INTERVENTION, RANDOMIZATION, AND BLINDING  
Patients were randomized 1:1 at the time of surgery into two groups based on the type 
irrigation to be used with intraoperative cystoscopy: control (normal saline) or antibiotic 
(Neosporin G.U. [200,000 U polymyxin B sulfate +40 mg neomycin sulfate] in 1 L NS). The 
randomization scheme was assigned by a statistician using randomization software in blocks of 
10. Allocation was concealed in an opaque envelope until the time of randomization. The 
patients and attending surgeon, who performed all evaluation and treatment of postoperative 
UTIs, remained blinded. Neosporin G.U. (Pfizer, 200,000 U polymyxin B sulfate 40 mg neomycin 
sulfate) is Food and Drug Administration approved for short-term use as a bladder irrigant to 
prevent bacteriuria associated with the use of indwelling catheters.2 The prepared solution is 
completely clear, bactericidal, and used as indicated, neomycin and polymyxin B are absorbed 
in clinically insignificant quantities.2 A neomycin or polymyxin solution was used in Hares' 1981 
cystoscopy irrigation study, has been used successfully in spinal cord injury patients with 
bacteriuria, and is well tolerated.3,4,5 Additionally, the medication is inexpensive and readily 
available in our operating room pyxis.  
 
 
 
 


STUDY PROTOCOL  
At the time of surgery, the randomization allocation envelope was opened by the surgical 
fellow. If indicated, this individual prepared the antibiotic solution by injecting 1 ml of neomycin 
or polymyxin into 1 L normal saline. The fellow remained independent of postoperative UTI 
diagnosis and treatment for study participants. The steps of the surgery remained standard; the 
study protocol made no alterations to usual care involving patient preparation, intravenous 
antibiotics, and instrumentation. We routinely use cefazolin for antibiotic prophylaxis for all 
surgeries, with the addition of metronidazole for hysterectomy in premenopausal patients, 
except in the case of associated allergies. Upon routine urinary catheter insertion, a urine 
sample was collected and sent for culture. Patients with a positive intraoperative urine culture 
were later excluded from analysis.  
 
Intraoperative cystoscopy was performed in normal fashion with the previously designated bag 
of irrigation fluid. At the completion of cystoscopy, the bladder was drained as per standard 
operating procedure. To determine the volume of fluid used during cystoscopy, the fluid bag 
was weighed before surgery and again after cystoscopy. A foley catheter was replaced per 
surgeon discretion. Upon hospital discharge, standardized post- operative instructions were 
given to all patients, including signs and symptoms of infections or other concerning 
postoperative sequelae.  
 
Postoperatively, patients were called at three time points (3 days, 2 weeks, and 4 weeks after 
surgery) to assess for urinary complaints and adverse events, including patient-reported 
diagnosis and treatment of UTI. Subjects were treated for postoperative UTI per attending 
surgeon discretion.  
 
OUTCOME MEASUREMENTS  
The primary outcome was the rate of postoperative UTI within 6 weeks after surgery. The 
Center for Disease Control and Prevention's definition of a symptomatic UTI was adapted to 
include the following: (1) at least one sign or symptom accompanied by positive urine culture 
with ≥105 colony-forming units/ml, (2) symptomatic UTI with clinician decision to treat as 
reported by the patient, or (3) at least one sign or symptom with positive urine dipstick (UA).6 
Timing of diagnosis was recorded as either the date of the positive urine culture or the timing 
of the postoperative phone call when the patient reported treatment of a UTI (3 days, 2 weeks, 
or 4 weeks after surgery). A sensitivity analysis was performed of UTIs treated within 2 weeks of 
surgery and any adverse effects related to the use of antibiotic irrigation. We also evaluated 
outcomes in the subgroup who had a vaginal prolapse repair procedure, which was previously  
reported to be at highest risk for postoperative UTI.7  
 
STATISTICAL ANALYSIS  
Based on 20.3% incidence of postoperative UTI,8 we determined that a sample size of 186 
would provide 80% power to detect a 50% absolute reduction in postoperative UTI rates at a 
two-sided α = .05. To account for an estimated 30% dropout rate with positive intraoperative 
urine culture or loss to follow up, we adjusted the total sample size to 242 patients total, with 
121 subjects in each study arm.  


Data was collected in our institutional REDCap database, and statistical analysis was performed 
with Stata version 15.1 (StataCorp). Covariates included in the analysis were patient-specific 
characteristics and medical comorbidities (age, race, obesity, smoking status, menopausal 
status, and history of Type 2 diabetes, recurrent UTIs, thyroid disease, asthma, hypertension, 
reflux dis- ease, depression, or anxiety) and volume of cystoscopy fluid used. Surgeries were 
characterized as primary vaginal or laparoscopic, and all concurrent procedures were noted. 
The randomized groups were compared using Pearson's χ2 test for categorical variables and the 
Student's t test for normally distributed continuous variables. Multivariable logistic regression 
analysis was used to adjust for possible confounding variables impacting the effect of antibiotic 
irrigation on postoperative UTI rates. Covariates significant on univariate analysis with p < .2 or 
with notable clinical relevance were included in the logistic regression. All results yielding p < 
.05 were deemed statistically significant.  
 
 
 
 
 
FOOTNOTES 
1. Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 statement: updated guidelines 
for reporting parallel group randomised trials. BMJ. 2010;340:c332. 
2. NEOSPORIN G.U. Neomycin sulfate and polymyxin b sulfate irrigant. Pfizer Laboratories 
Div Pfizer Inc. 2016. https://www.pfizer.com/products/product-detail/neosporin_ 
g_u_irrigant 
3. Huen KH, Nik-Ahd F, Chen L, Lerman S, Singer J. Neomycin–polymyxin or gentamicin 
bladder instillations decrease symptomatic urinary tract infections in neurogenic 
bladder patients on clean intermittent catheterization. J Pediatr Urol. 
2019;15(2):178.e171-178.e177. 
4. Linsenmeyer TA, Jain A, Thompson BW. Effectiveness of neomycin/polymyxin bladder 
irrigation to treat resistant ur- inary pathogens in those with spinal cord injury. J Spinal 
Cord Med. 1999;22(4):252-257. 
5. Waites KB, Canupp KC, Roper JF, Camp SM, Chen Y. Eva- luation of 3 methods of bladder 
irrigation to treat bacteriuria in persons with neurogenic bladder. J Spinal Cord Med. 
2006; 29(3):217-226. 
6. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-
associated infection and criteria for specific types of infections in the acute care setting. 
Am J Infect Control. 2008;36(5):309-332. 
7. El-Nashar SA, Schmitt JJ, Arora C, JB, Occhino JA. Urinary tract infection after 
hysterectomy for benign gynecologic conditions or pelvic reconstructive surgery. Obstet 
Gynecol. 2018;132(6):1347-1357. 
8. Unger CA, Walters MD, Ridgeway B, Jelovsek JE, Barber MD, Paraiso MF. Incidence of 
adverse events after uterosacral colpopexy for uterovaginal and posthysterectomy vault 
pro- lapse. Am J Obstet Gynecol. 2015;212(5):603.e601-607.