Clinical trial NCT03080389: Sensitivity of Extended Cultures in Diagnosing Urinary Tract Infections
Official title: Are Extended Urine Cultures More Sensitive Than Standard Urine Cultures in Diagnosing Urinary Tract Infections in Patients With Urgency and Frequency?
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Overactive Bladder
Overactive Detrusor
Urgency-Frequency Syndrome
UTI
Keywords: overactive bladder
overactive detrusor
urgency-frequency
urinary tract infection
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2017-03-15
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be included in the study if they have a history of overactive bladder or urgency and frequency with or without incontinence, they must be female, able to speak English, and must be 18 years old or older and able to provide informed consent. Patients must have a PUF score of less than or equal to 4 and answer "a moderate amount" or "a lot" on the Bother questionnaire number 2 or 3. They must also not be a prisoner. Patients will be excluded if they have are pregnant, have urinary retention, greater than stage 2 prolapse, renal calculi, immune-suppressed, those with neurologic disorders, prior use of antibiotics in the past month, had prior radiation to the pelvic floor, or chronic pelvic pain defined by more than 6 months of pelvic pain, or dysuria.

Brief summary: There is some evidence to suggest standard urine cultures may not be adequate in identifying patients with low grade urinary tract infections. Therefore, there are patients with symptoms of frequency and urgency, being misdiagnosed with overactive bladder due to negative urine cultures. If this is true, could extended cultures be used to identify the false negative patients?

Detailed description: In 2014, Hilt, Evann et al published a study called "Urine is not sterile," in which it was found via PCR and extended urine cultures, there is a microbiome that exists within the urinary bladder. In this study, 92% of the bacteria failed to be identified by a standard urine culture but 80% were identified with extended urine cultures. In further explorations of the significance of this microbiome, Pearce, Meghan et al. found that the female bladder consists of increased abundance of bacteria in patients with UUI; including Gardnerella and Lactobacilus gasseri. Then in 2015, a study by Thomas-White, Krystal et al. found that patients with urge urinary incontinence (UUI) who responded to treatment with Solifenacin had fewer and less diverse communities of bacteria when evaluated by PCR and extended urine cultures.

The clinical significance of the bacteria identified is not well understood. However, these studies show that the presence of bacteria is being missed by standard cultures. Dune et al. found that of patients with UTI symptoms, 27.5% were standard culture negative but extended quantitative urine culture positive. This demonstrates that practitioners may be overlooking urinary tract infections in patients with frequency and urgency. Therefore, if bacteria within the urine can be detected with extended cultures, can this technique be used to improve detection and treatment of urinary infections in patients with symptoms of frequency and urgency?

The hypotheses states that extended urine cultures are more sensitive in the identification of urinary tract infections in patients with symptoms of urgency and frequency. The secondary hypothesis is that treatment of the uropathogen identified on extended urine cultures will improve patient symptoms.

Eligibility criteria: Inclusion Criteria:

* 18 y/o-70 y/o
* Able to consent
* Urgency /Frequency
* Urge incontinence
* PUF score ≤ 4
* Bother questionnaire #2 or #3 answered either "a moderate amount" or "a lot"

Exclusion Criteria:

* Pregnant
* Pelvic radiation
* Chronic pelvic pain
* Urinary retention
* Greater than Stage 2 prolapse
* Renal calculi
* Recurrent UTI (2 in 6 months)
* Immunosuppressed
* Neurologic disorder
* No antibiotics in the past 4 weeks

Primary outcomes:
measure: Sensitivity of extended urine cultures compared to standard urine cultures.
timeFrame: one year
Secondary outcomes:
measure: Treatment of uropathogens found on extended cultures result in negative repeat extended urine culture.
timeFrame: one year
measure: Treatment of uropathogens found on extended cultures improves urinary tract symptoms measured by the Bother and UDI-6 questionnaires
timeFrame: one year
Other outcomes:
Locations:
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
Study officials:
affiliation: Cleveland Clinic Florida
name: Eric Hurtado, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger PC. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014 Mar;52(3):871-6. doi: 10.1128/JCM.02876-13. Epub 2013 Dec 26.
citation: Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, Wolfe AJ. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14. doi: 10.1128/mBio.01283-14.
citation: Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, Zilliox MJ, Brincat C, Price TK, Kuffel G, Schreckenberger P, Gai X, Brubaker L, Wolfe AJ. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2016 May;27(5):723-33. doi: 10.1007/s00192-015-2847-x. Epub 2015 Sep 30.
citation: Tanaka Dune, Evann Hilt, Travis Price, Colleen Fitzgerald, Cynthia Brincat, Linda Brubaker, Alan J. Wolfe, Paul Schreckenberger, Elizabeth R. Mueller. False negatives of standard urine cultures may delay patient treatment. AUGS. October 13-17, 2015.