Sensitivity of Extended Cultures in Diagnosing Urinary Tract Infections

NCT ID: NCT03080389

Last Updated: 2018-09-04

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 16 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2018-08-01

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.

Conditions

Overactive Bladder; Overactive Detrusor; Urgency-Frequency Syndrome; UTI

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Extended urine culture

Each patient will be their own control and two specimens will be obtained from each participant. The first will be a catheterized urine sample to be sent for routine culture and the second will be collected from the same catheterized specimen and sent for extended culture.

Extended Urine Culture

Intervention Type: PROCEDURE

Extended Urine Culture Standard cultures will include 0.001 ml of specimen plated on sheep blood agar and MacConkey agar. Plates were inoculated and incubated at 35 degrees Celsius for 24 hours. Samples were considered positive if there were 10^3 cfu or greater. The extended urine culture will be spun down by centrifuge (3000 rpm for 5 min) and 0.1 ml of the sediment will be cultured for 48 hours.

The participants will fill out the Bother, UDI-6, and PUF questionnaires before the cultures. If a patient has a positive urine culture, the patient will be asked to repeat the questionnaires 7-30 days post treatment with antibiotics. A comparison will be made between the standard and extended urine cultures to assess for a difference in identification and treatment of uropathogens.

Interventions

Extended Urine Culture

Extended Urine Culture Standard cultures will include 0.001 ml of specimen plated on sheep blood agar and MacConkey agar. Plates were inoculated and incubated at 35 degrees Celsius for 24 hours. Samples were considered positive if there were 10^3 cfu or greater. The extended urine culture will be spun down by centrifuge (3000 rpm for 5 min) and 0.1 ml of the sediment will be cultured for 48 hours.

The participants will fill out the Bother, UDI-6, and PUF questionnaires before the cultures. If a patient has a positive urine culture, the patient will be asked to repeat the questionnaires 7-30 days post treatment with antibiotics. A comparison will be made between the standard and extended urine cultures to assess for a difference in identification and treatment of uropathogens.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Eric Hurtado

Urogynecology Staff

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eric Hurtado, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Florida

Locations

Cleveland Clinic Florida

Weston, Florida, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 24371246 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25006228 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26423260 (View on PubMed)

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.

Reference Type: BACKGROUND

Other Identifiers

FLA 16-108

Identifier Type: -

Identifier Source: org_study_id