Conditions: Urinary Tract Infections Urinary Retention Postoperative Pelvic Organ Prolapse
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 185
Healthy volunteers: no

Brief summary:
This study is randomized double-blinded placebo-controlled trial to access oral Methenamine Hippurate (MH) in combination with cranberry capsules is superior to cranberry capsules alone in prevention of UTI in patients with transient post-operative urinary retention requiring a Foley catheter after pelvic reconstructive surgery.

Detailed description:
Urinary tract infections (UTIs) are one of the most common bacterial infections in women. It is estimated that 1.6 billion dollars are spent on UTI treatment each year. Antibiotics have been the mainstay of treatment of UTIs, however frequent use has increased the prevalence of antibiotic resistant organisms. Therefore, focus has shifted to non-antibiotic therapy for UTI prophylaxis.

Methenamine Hippurate (MH) has been studied for decades due to its potential role in prevention of UTI. While not technically an antibiotic, MH works via its bacteriostatic action in the bladder. Benefits of MH are the lack of development of resistance, and the selective nature of this drug to the urinary system only. However, MH is best used in conjunction with an acidifying agent to increase its bioavailability (such as cranberry capsules or other acidic products). The usage of MH has been studied in various populations, has been seen to be effective in short-term catheterization. Usage of cranberry as prophylaxis for UTI is controversial; however, results have been favorable in the post-operative gynecological population.

Post-operative urinary retention (POUR) occurs frequently in patients who undergo incontinence and pelvic prolapse surgery. Although the definition of POUR can vary between clinicians, it is reported as 2.5-24% to as high as 43% after tension-free transvaginal mesh sling placement. This population is at also at high risk for UTI due to advanced age and menopausal status. Moreover, using a catheter longer than 2 days incurs a 2-fold increased risk of development of UTI with an estimated 5% increase in bacteriuria each day of catheterization.

In hopes to decrease the overuse of antibiotics and decrease the likelihood of antibiotic resistance, we propose that the use of MH and cranberry can reflect a potential benefit in this population of short-term indwelling Foley catheter use and help reduce the incidence of post-operative UTI after pelvic surgery.

The patients will then be randomized to either receive cranberry capsules and placebo OR cranberry capsules and Methenamine Hippurate.

Arms:
arm 1: Subjects will be instructed to take Methenamine Hippurate 1 g tablet ( 1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. arm 2: Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days.

Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016.

Interventions: intervention 1: Methenamine Hippurate 1 g tablet intervention 2: Placebo tablet
Intervention descriptions: intervention 1: Methenamine Hippurate (study drug) is an FDA approved medication in the prevention of UTI. Methenamine Hippurate 1g contains Hippuric acid salt of Methenamine (hexamethylene tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, FD\&C Yellow No. 5 (tartrazine) (www.iodine.com/drug/hiprex/fda-package-insert). intervention 2: Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient.

Protocol document:
Prot_SAP_000.pdf: 
 
Template version: 10/16/15 
RESEARCH PROTOCOL 
 
Date 
2/20/21 
Title 
Methenamine Hippurate with Cranberry Capsules versus 
Cranberry Capsules alone for UTI prevention in a short-term 
indwelling Foley catheter population after Urogynecological 
surgery:  A Double-Blinded Randomized Controlled Trial 
Principal Investigator 
Rachel Pauls, MD 
Sub-Investigators 
Catrina C. Crisp, MD MSc; Jennifer Yeung, DO; Emily Aldrich, MD 
Research Specialist 
Eunsun Yook, MS 
Department 
Department of OB/Gyn, Division of Urogynecology and 
Reconstructive Pelvic Surgery 
Hatton # 
18-115 
IRB Review Type: 
 
 Exempt 
 
 Expedited  
 Full Board 
 
Purpose of Study    
• Primary Aim: To assess if oral Methenamine Hippurate (MH) in combination with 
cranberry capsules is superior to cranberry capsules alone in prevention of UTI in 
patients with transient post-operative urinary retention requiring a Foley catheter after 
pelvic reconstructive surgery.  
o Secondary Aims:  
▪ To assess patient adherence to the interventions. 
▪ To assess patient satisfaction associated with the different interventions. 
 
Hypothesis or Research Question  
• We hypothesize that daily oral MH and cranberry therapy will be a superior treatment 
to cranberry alone in the prevention of UTI in patients with short term indwelling Foley 
catheters after pelvic reconstructive surgery.  
 
Background 
Urinary tract infections (UTIs) are one of the most common bacterial infections in women [1]. It 
is estimated that 1.6 billion dollars are spent on UTI treatment each year [2-3]. Escherichia coli 
(E.coli), a gram negative bacterium, is the most common pathogen found amongst those 
diagnosed with UTIs. Research suggests that 70-95% of UTIs are attributed to E.coli which 
originates from intestinal microflora [4-7]. Additionally, the more virulent strains of E.coli 
express type 1 and p-fimbriae, which aid in adhesion to the urothelium [8-12]. Antibiotics have 
been the mainstay of treatment of UTIs, however frequent use has increased the prevalence of 
antibiotic resistant organisms [3-4]. Therefore, focus has shifted to non-antibiotic therapy for 
UTI prophylaxis.  
 
Methenamine Hippurate (MH) has been studied for decades due to its potential role in 
prevention of UTI. While not technically an antibiotic, MH works via its bacteriostatic action in 
the bladder.  MH’s breakdown products include ammonium and formaldehyde [13-15] which 


 
Template version: 10/16/15 
are most effective at a urine pH below 5.5 [16-18].  Benefits of MH are the lack of development 
of resistance, and the selective nature of this drug to the urinary system only.  However, MH is 
best used in conjunction with an acidifying agent to increase its bioavailability (such as 
cranberry capsules or other acidic products) [14-18]. 
 
The usage of MH has been studied in various populations, has been seen to be effective in 
short-term catheterization [15]. One study by Schiotz, et. al revealed that in patients after 
gynecological surgery that required 24 hours of Foley catheter placement had an incidence of 
UTI in 13.9% of patients with placebo versus 2.7% of patients using MH [19]. Although there is 
some evidence of benefit, a Cochrane Database review revealed there was significant 
heterogeneity between studies and many of these studies vary in aspects such as definition of 
UTI and dosage of MH. Many prior studies did not combine MH with an acidifying agent, which 
could also limit its efficacy [14].  
 
The American cranberry (Vaccinium macrocarpon) is another non-antibacterial agent which has 
been widely studied [8]. Cranberries are composed of ingredients that include fructose, 
anthocyanidins and proanthocyanidins [8, 20]. These components are proposed to affect 
adhesion proteins that are expressed by bacteria, such as E.coli, and prevent the development 
of infection [8, 20, 28-30].   
 
Usage of cranberry as prophylaxis for UTI is controversial; however, results have been favorable 
in the post-operative gynecological population. One such study by Foxman et al. revealed that 
the incidence of UTI was significantly lower in the cranberry than placebo group (19% versus 
38%) after undergoing gynecological surgery [32]. Additionally, the 7 patients who required an 
indwelling catheter at time of discharge were found to have lower rates of UTI than placebo (1 
of 3 versus 3 of 4, respectively) [32]. However, a study from our center revealed that real-time 
prescriptions of cranberry to postoperative patients with catheters did not significantly reduce 
UTI rates [33]. 
 
Post-operative urinary retention (POUR) occurs frequently in patients who undergo 
incontinence and pelvic prolapse surgery [34-36]. Although the definition of POUR can vary 
between clinicians, it is reported as 2.5-24% to as high as 43% after tension-free transvaginal 
mesh sling placement [34, 36, 37]. This population is at also at high risk for UTI due to advanced 
age and menopausal status [34, 38, 39]. Finally, using a catheter longer than 2 days incurs a 2-
fold increased risk of development of UTI with an estimated 5% increase in bacteriuria each day 
of catheterization [32, 34, 40-41].  
 
Moreover, although the incidence of UTI after pelvic reconstructive surgery ranges from 10% to 
64% [42], a retrospective review performed at our institution revealed our incidence of UTI was 
as high as 72% [33]. In hopes to decrease the overuse of antibiotics and decrease the likelihood 
of antibiotic resistance, we propose that the use of MH and cranberry can reflect a potential 
benefit in this population of short-term indwelling Foley catheter use and help reduce the 
incidence of post-operative UTI after pelvic surgery.  
    


 
Template version: 10/16/15 
Research Plan  
• Study Design  
o Randomized double-blinded placebo-controlled trial  
• Setting for the study 
o All patients will be approached for enrollment into the study if they fail their 
retrograde void trial (VT) after major pelvic reconstructive surgery for pelvic 
organ prolapse during their hospital stay 
o The patients will then be randomized to either receive cranberry capsules and 
placebo OR cranberry capsules and Methenamine Hippurate.  
o The research nurse will be blinded to the group allocation.  
o Patients will be instructed to take the pills assigned to them twice daily until 
their repeat retrograde VT in the office (6-8 days). 
o A catheterized urine specimen will be then collected on the day of the 
retrograde void trial on or about postoperative day 7. 
o Patients will be asked to return the pill bottles at their catheter removal visit, on 
or about postoperative day 7. 
o At the end of the retrograde VT, patients will be given a questionnaire to 
complete regarding their experience with the medication randomized to them 
and satisfaction with the medication.  
o At 2 weeks postoperatively, the patients will have a clean-catch urine specimen 
during their routine postoperative visit and this will be recorded. 
o Patients’ charts will be followed until their 6-week post-operative visit. 
o  Symptomatic  or culture proven urinary tract infections detected during the 
research period will be treated with the appropriate antibiotics as standard of 
care, based on the judgment of the treating provider.  
 
• Participants 
Study population is women between 18 years old and 90 years old.    
 
Inclusion Criteria: 
• Patients who undergo major pelvic organ prolapse surgery that are 
diagnosed with POUR via failed retrograde void trial and require an 
indwelling Foley catheter upon hospital discharge.  
 
 
Exclusion Criteria: 
▪ Unwillingness to participate in the study. 
▪ Inability to understand English. 
▪ Pregnant women 
▪ Patient personal history of nephrolithiasis, urogenital anomaly, 
neurogenic bladder, chronic renal insufficiency (GFR <60 ml/min/1.73 m²) 
, sarcoidosis, and severe hepatic insufficiency.  
▪ Currently (prior 3 months) undergoing medical management for 
recurrent UTI or interstitial cystitis 
▪ Current antibiotic use over the last month for additional medical issues. 


 
Template version: 10/16/15 
▪ Active urinary tract infection.  
▪ Patient history of taking Warfarin (Coumadin).  
▪ Intraoperative bladder injury or cystotomy 
▪ Physical or mental impairment that would affect the subject’s ability to 
take medications daily or fill out questionnaires.  
▪ Reported allergy to any of the ingredients in the cranberry, MH, or 
placebo pill  
o Sample Size 
▪ A sample size was calculated to be 88 patients in each arm based on the 
following: 
• A prior study by Foxman et al. evaluated incidence of UTI of 
patients who underwent various benign gynecological surgeries 
who had placement of an indwelling urinary catheter. These 
patients were randomized to either receive TheraCran cranberry 
capsules or placebo for 6-8 weeks duration [32]. 
• Two group χ² test with a 0.050 two-sided significance level was 
used for sample size calculation.  
• The power was set to 80% 
• Assuming an estimated drop-out rate of 15%, the number of 
patient enrollment per arm was set to 104, for a total of 208 
patients total 
 
• Data Collection 
o Primary Outcome: 
▪  Incidence of UTIs requiring treatment in each group, diagnosed during 
the first (approximately) one week of short-term indwelling Foley 
catheter in the post-operative period after undergoing major pelvic 
reconstructive surgery.  
o Secondary Outcome:  
▪ Adherence to the medication regimen provided  
▪ Patient satisfaction with medication regimen provided 
▪ Adverse effects that patients encountered during study period  
▪ Number of patients who are diagnosed and treated for UTI in the 6-week 
post-operative period following surgery 
o General Demographic Data:  
▪ Age, weight, height, BMI, ethnicity, past medical history, social history, 
preoperative stage of prolapse (POPQ),  type of surgical procedure, 
duration of Foley catheter therapy, post-operative complications, UTI 


 
Template version: 10/16/15 
symptoms, urine acidity (pH), diagnosis of overactive bladder, post void 
residual (PVR) before surgery, POD1 and on or about POD7.   
• Intervention or experimental aspect of the study 
o All patients of Cincinnati Urogynecology Associates who undergo pelvic organ 
prolapse repair(s) and have a retrograde VT prior to discharge per standard 
practice. The retrograde VT will be performed by the nursing staff. Per protocol, 
up to 300ml sterile saline will be instilled into the bladder and the indwelling 
urinary catheter will be removed. Patients will be allotted 30 minutes to void. 
The instilled volume, voided volume, and PVR if needed will be recorded. 
o Failure of the retrograde VT is defined by inability to void two-thirds of the 
instilled volume or PVR greater than 100mL. 
o Patients who fail the retrograde VT will then be approached for the study by one 
of the investigators or trained Research Nurse.  
o An indwelling urinary catheter will be reinserted and the patient will be taught 
on its use and care by the nursing staff.  
o If the patient agrees to participate in the study, the patient will be randomized to 
either receive either the MH and Cranberry or Cranberry and placebo.  
o Based on a randomization list, the patient will be assigned a Study ID and the 
medications will be distributed by the inpatient pharmacy to the patient prior to 
their discharge. 
o The medications will have a label which will be generated by the pharmacy that 
includes the name of the patient, name of the medication group allocation, (Ex. 
Med A) expiration date and study ID. 
o These medications will be added onto their discharge instructions via a 
Medication Reconciliation on EPIC.  
o All subjects will be provided all other routine prescriptions for pain medication, 
bowel regimen and instructions on how to administer the medication given.   
o Patients will be advised to take the medication roughly at the same time each 
day with food to aid in absorption.  
o On or about POD7, the patient will be asked to return to the office for a repeat 
retrograde VT (as described above).  
o A catheterized urine specimen will be collected on this visit and recorded. 
o If the patient fails the retrograde VT on or about POD7 they will have the 
catheter replaced. Additionally, they will be recommended to continue 
Cranberry supplementation as per our current routine practices until they return 
on their two-week postoperative visit to repeat the retrograde VT (as described 
above). They will however not be asked to continue MH or the placebo pills 
during this time. 


 
Template version: 10/16/15 
o Patients will fill out a questionnaire based on the Medicine Acceptability 
Questionnaire as well as UTI symptoms experienced and overall satisfaction [43].  
• Two-week postoperative visit  
o All patients will have a routine examination at 2 weeks with a clean catch urine 
specimen 
o All patients will have urine dip performed on the PVR urine sample. If positive for 
leukocyte esterase, white blood cells, or nitrites, the urine dip will be sent to the 
laboratory for culture. All urine culture results will be reviewed and if positive, 
will be treated and recorded.  
• Six-week postoperative visit  
o All patients will be asked to present for routine 6-week post-operative visit. 
 
• As per standard practice at our office, patients will be advised to  report symptoms 
such as dysuria, fever, flank pain, hematuria, frequency or urgency, cloudy urine, 
hematuria, or abdominal pain,.  During business hours they will be asked to call the 
office staff, while other times they will page the on-call physician. 
• During operating hours, the office staff will arrange a clinic visit for the same day at 
one of four outpatient clinics (Clifton, West Chester, Kenwood, Anderson) and 
obtain a urine sample prior to the start of antibiotic therapy.  
• If not during office hours, the on-call staff will either direct the patient to a facility 
for urine collection prior to the start of antibiotic therapy, or if unable to do so, start 
antibiotic therapy based on clinical symptoms.  
• During any antibiotic therapy the patients will be advised to STOP all study 
medications  
• All of these encounters will be recorded.   
o Experimental oral capsules 
▪ Methenamine Hippurate 1g (1 tablet BID)  
• Contains Hippuric acid salt of Methenamine (hexamethylene 
tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, 
FD&C Yellow No. 5 (Tartazine) [44]. 
• >90% of methenamine is excreted in the urine within 24 hours 
after administration [44].  
• Side effects are generally mild and are found in 3.3% of patients. 
These include gastrointestinal upset, dysuria, abdominal cramps, 
and rash which are reversible [44].  
• Sulfonamides are to be used with caution with Methenamine as it 
has been shown that it concurrent use may cause a decrease in 
efficacy of the Methenamine by alkalization of the urine [44]. 
▪ Placebo Pill 


 
Template version: 10/16/15 
▪ Nature Made Super Strength Cranberry 450mg Extract (1 Tablet BID) 
• Side effects are generally mild and include stomach/abdominal 
upset, diarrhea. Kidney stones may occur but is associated with 
higher high doses [46]. 
• There have been case reports regarding hypercoagulability with 
high doses of Cranberry concomitant Warfarin therapy [47]. 
 
o Urinary Tract Infection (UTI) [48] 
• Definition will include bacteriuria will be presence of bacteria at 
clinically relevant levels, or treatment with antibiotic for 
suspected UTI by a provider 
o Possible associated symptoms patients may complain of 
include: dysuria, suprapubic pressure/pain, fever >100.4, 
urinary frequency or urgency.  
 
• Statistical Analysis 
o Descriptive statistics will be generated for demographic information such as age, 
race, BMI etc. Chi-squared test or Fisher’s exact test will be employed to 
examine the difference in categorical variables between two groups.  A Shapiro-
Wilk test will be performed for testing normality. To test the difference in 
continuous variables between two groups, Student t-test or a Mann-Whitney 
test will be used. A Logistic regression will be implemented to calculate the odds 
ratio and corresponding confidence interval for comparing the incidence of UTI 
between two groups.  
 
Ethical Considerations 
• Informed consent  
o Patients who agree to participate in the study will sign a written informed 
consent. They will be consented by one of the stated investigators or trained 
Research Nurse and they will receive a copy of the signed informed consent 
statements (ICS). A copy will be put in their medical file. 
• Privacy information 
o Extensive efforts will be made to ensure and maintain participant 
confidentiality. All identifying information will be maintained in a secure area 
at all times. Source documentation will be maintained in a separate folder. 
When documentation has to be made available for data analysis, copies of 
the source (Excel spreadsheets) with only Subject ID number visible and 
personal information obscured will be used. All communication between 
staff members regarding participant data will occur via the Subject ID 
number only. However, identifying information will be retained in the 
original/source documents. 


 
Template version: 10/16/15 
o The participant will be logged in the Excel spreadsheet and assigned a 
Subject ID number. Each participant will be assigned the next available 
Subject ID number. Once each Subject ID number has been assigned, it will 
not be reassigned. The Excel spreadsheet will be stored on a password 
protected, encrypted TriHealth computer for ten years following study 
closure, and then purged. 
 
Estimated Period of Time to Complete Study 
When will study begin? 
June 2019 
Protocol Development 
Completed 
December 18, 2018  
Admin Review Time 
2 weeks  
IRB Approval 
January 8th, 2018  
Data collection 
Subjects to be enrolled starting June 2019 
Data analysis 
January 2021  
 
• When and how will results be disseminated? 
▪ Submit for abstract presentation at national/international meeting and 
publication 
 
 
References 
[1] Leckie, K. What is the evidence for the role of oestrogen in the prevention of recurrent 
urinary tract infections in postmenopausal women? An evidence-based review. Journal of 
Clinical Gerontology and Geriatrics.2010 Dec; 1(2):31-35. 
[2] Foxman B. Epidemiology of urinary tract infections: Incidence, morbidity and economic 
costs. Am J of Med. 2002;113:5S-13S [PubMed:12113866] 
[3] Borchert, D, et al. “Prevention and Treatment of Urinary Tract Infection with Probiotics: 
Review and Research Perspective.” Indian Journal of Urology, vol. 24, no. 2, 2008, p. 139., 
doi:10.4103/0970-1591.40604. 
[4] Ng, Qin Xiang, et al. “Use of Lactobacillus Spp. to Prevent Recurrent Urinary Tract Infections 
in Females.” Medical Hypotheses, vol. 114, 2018, pp. 49–54., doi:10.1016/j.mehy.2018.03.001. 
[5] Bartoletti, Riccardo, et al. “Treatment of Urinary Tract Infections and Antibiotic 
Stewardship.” European Urology Supplements, vol. 15, no. 4, 2016, pp. 81–87., 
doi:10.1016/j.eursup.2016.04.003. 
[6] Vahlensieck, Winfried, et al. “Management of Uncomplicated Recurrent Urinary Tract 
Infections.” European Urology Supplements, vol. 15, no. 4, 2016, pp. 95–101., 
doi:10.1016/j.eursup.2016.04.007. 
[7] Köves, Béla, and Björn Wullt. “The Roles of the Host and the Pathogens in Urinary Tract 
Infections.” European Urology Supplements, vol. 15, no. 4, 2016, pp. 88–94., 
doi:10.1016/j.eursup.2016.04.005. 


 
Template version: 10/16/15 
[8] Hisano, M, et al. “Cranberries and Lower Urinary Tract Infection Prevention.” Clinics, vol. 67, 
no. 6, Dec. 2012, pp. 661–667., doi:10.6061/clinics/2012(06)18. 
[9]. Schmidt DR, Sobota AE. An examination of the anti-adherence activity of cranberry juice on 
urinary and nonurinary bacterial isolates. Microbios. 1988;55(224-225):173–81.  [PubMed] 
[10] Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on 
adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob 
Agents Chemother. 1989;33(1):92–8. [PMC free article]  [PubMed] 
[11]Pinzon-Arango PA, Liu Y, Camesano TA. Role of cranberry on bacterial adhesion forces and 
implications for Escherichia coli-uroepithelial cell attachment. J Med Food. 2009;12(2):259–
70.  [PubMed] 
[12]Ofek I, Mirelman D, Sharon N. Adherence of Escherichia coli to human mucosal cells 
mediated by mannose receptors. Nature. 1977;265(5595):623–5.  [PubMed] 
[13] Saint, Sanjay, and Benjamin A. Lipsky. “Preventing Catheter-Related Bacteriuria.” Archives 
of Internal Medicine, vol. 159, no. 8, 1999, p. 800., doi:10.1001/archinte.159.8.800. 
[14] Lee, B, et al. “Methenamine Hippurate for Preventing Urinary Tract Infections.” The 
Cochrane Database of Systematic Reviews (Protocol), 2002, doi:10.1002/14651858.cd003265. 
[15] Bennett, John E., et al. Mandell, Douglas, and Bennetts Principles and Practice of Infectious 
Diseases. Elsevier / Saunders, 2015. 
[16] Greenwood, D., and R. C. B. Slack. “The Antibacterial Activity of Hexamine (Methenamine), 
Hexamine Hippurate and Hexamine Mandelate.” Infection, vol. 9, no. 5, 1981, pp. 223–227., 
doi:10.1007/bf01640720. 
[17] Hetey SK. Effect of ascorbic acid on urine pH in patients with injured spinal cords. American 
Journal of Hospital Pharmacy 1990;37(2):235-7. 
[18] Wall I, Tiselius HG. Long-term acidification of urine in patients treated for infected renal 
stones. Urologia Internationalis 1990;45(6):336-41.  
[19] Schiotz, Hjalmar A., and Kristian Guttu. “Value of Urinary Prophylaxis with Methenamine in 
Gynecologic Surgery.” Acta Obstetricia Et Gynecologica Scandinavica, vol. 81, no. 8, 2002, pp. 
743–746., doi:10.1034/j.1600-0412.2002.810810.x. 
[20] Guay DR. Cranberry and urinary tract infections. Drugs. 2009;69(7):775–807.  [PubMed] 
[21]Bruyere F. [Use of cranberry in chronic urinary tract infections] Med Mal 
Infect. 2006;36(7):358–63.[PubMed] 
[22]Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of 
cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract 
infections in women. BMJ. 2001;322(7302):1571. [PMC free article]  [PubMed] 
[23]Jepson RG, Craig JC. A systematic review of the evidence for cranberries and blueberries in 
UTI prevention. Mol Nutr Food Res. 2007;51(6):738–45.  [PubMed] 
[24]Cimolai N, Cimolai T. The cranberry and the urinary tract. Eur J Clin Microbiol Infect 
Dis. 2007;26(11):767–76.  [PubMed] 
[25]Gupta K, Chou MY, Howell A, Wobbe C, Grady R, Stapleton AE. Cranberry products inhibit 
adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial 
cells. J Urol. 2007;177(6):2357–[26][PMC free article]  [PubMed] 
[27]Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, et al. Reduction of 
Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a 


 
Template version: 10/16/15 
double-blind randomized placebo-controlled cross-over trial. World J Urol. 2006;24(1):21–
7.  [PubMed] 
[28] Foo LY, Lu Y, Howell AB, Vorsa N. The structure of cranberry proanthocyanidins which 
inhibit adherence of uropathogenic P-fimbriated Escherichia coli in 
vitro. Phytochemistry. 2000;54(2):173–81.[PubMed] 
[29]Howell AB, Vorsa N, Der Marderosian A, Foo LY. Inhibition of the adherence of P-fimbriated 
Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries. N 
Engl J Med. 1998;339(15):1085–6.  [PubMed] 
[30] Foo LY, Lu Y, Howell AB, Vorsa N. A-Type proanthocyanidin trimers from cranberry that 
inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod. 2000;63(9):1225–
8.  [PubMed] 
[31] Wang, Chih-Hung, et al. “Cranberry-Containing Products for Prevention of Urinary Tract 
Infections in Susceptible Populations.” Archives of Internal Medicine, vol. 172, no. 13, Sept. 
2012, doi:10.1001/archinternmed.2012.3004. 
[32] Foxman, Betsy, et al. “Cranberry Juice Capsules and Urinary Tract Infection after Surgery: 
Results of a Randomized Trial.” American Journal of Obstetrics and Gynecology, vol. 213, no. 2, 
2015, doi:10.1016/j.ajog.2015.04.003. 
[33] Shatkin-Margolis, Abigail, et al. “Cranberry Supplementation Does Not Reduce Urinary 
Tract Infections in Patients With Indwelling Catheters After Pelvic Reconstructive 
Surgery.” Female Pelvic Medicine & Reconstructive Surgery, vol. 24, no. 2, 2018, pp. 130–134., 
doi:10.1097/spv.0000000000000507. 
[34] Geller, Elizabeth J. “Prevention and Management of Postoperative Urinary Retention after 
Urogynecologic Surgery.” International Journal of Womens Health, 2014, p. 829., 
doi:10.2147/ijwh.s55383. 
[35] Buchko, Barbara L., and Leslie E. Robinson. “An Evidence-Based Approach to Decrase Early 
Post-Operative Urinary Retention Following Urogynecology Surgery.” Urologic Nursing, vol. 32, 
no. 5, 2012, p. 260., doi:10.7257/1053-816x.2012.32.5.260. 
[36]Dorflinger A, Monga A. Voiding dysfunction. Curr Opin Obstet Gynecol. 2001;13(5):507-512.  
[37] Partoll, Linda M. “Efficacy of Tension-Free Vaginal Tape with Other Pelvic Reconstructive 
Surgery.” American Journal of Obstetrics and Gynecology, vol. 186, no. 6, 2002, pp. 1292–1298., 
doi:10.1067/mob.2002.123736. 
[38] Wu, Jennifer M., et al. “Lifetime Risk of Stress Urinary Incontinence or Pelvic Organ 
Prolapse Surgery.” Obstetrics & Gynecology, vol. 123, no. 6, 2014, pp. 1201–1206., 
doi:10.1097/aog.0000000000000286. 
[39] Ketia H, et al. “Predictive Factors of Early Postoperative Urinary Retention in the 
Postanesthesia Care Unit.” Survey of Anesthesiology, vol. 49, no. 6, 2005, pp. 329–330., 
doi:10.1097/01.sa.0000185372.31470.db. 
[40] Wald, Heidi L. “Indwelling Urinary Catheter Use in the Postoperative Period.” Archives of 
Surgery, vol. 143, no. 6, 2008, p. 551., doi:10.1001/archsurg.143.6.551. 
[41]Maki DG, Tambyah PA. Engineering out the risk for infection with urinary catheters. Emerg 
Infect Dis 2001;7:342-7. 
[42] Falagas ME, Athanasiou S, Iavazzo C, et al. Urinary tract infections after pelvic floor 
gynecological surgery: prevalence and effect of antimicrobial prophylaxis. A systematic 
review. Int Urogynecol J Pelvic Floor Dysfunct 2008;19(8):1165–1172. 


 
Template version: 10/16/15 
[43] Estelle Payerne, Debi Bhattacharya. Identifying the factors that influence patient 
acceptability of oral medicines: a systematic review of literature. PROSPERO 2013 
CRD42013004033 Available 
from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42013004033 
[44] “Hiprex (Methenamine Hippurate) FDA Package Insert & Drug Facts.” Iodine, 
www.iodine.com/drug/hiprex/fda-package-insert. 
[45] “Calcium Carbonate Oral : Uses, Side Effects, Interactions, Pictures, Warnings & 
Dosing.” WebMD, WebMD, www.webmd.com/drugs/2/drug-579-139/calcium-carbonate-
oral/calcium-supplements-oral/details. 
[46] “TheraCran Side Effects in Detail.” Drugs.com, Drugs.com, www.drugs.com/sfx/theracran-
side-effects.html. 
[47] Paeng, Christine H., et al. “Interaction Between Warfarin and Cranberry Juice.” Clinical 
Therapeutics, vol. 29, no. 8, 2007, pp. 1730–1735., doi:10.1016/j.clinthera.2007.08.018. 
[48] Brubaker, Linda, et al. “American Urogynecologic Society Best-Practice Statement.” Female 
Pelvic Medicine & Reconstructive Surgery, 2018, p. 1., doi:10.1097/spv.0000000000000550.