Dipsticks and Microscopy to Reduce Antibiotic Use in Women's Urinary Tract Infections: a Pilot Trial (MicUTI) (MicUTI)

Dipsticks and Point-of-care Microscopy to Reduce Antibiotic Use in Women With Uncomplicated Urinary Tract Infections: a Cluster-randomized Controlled Pilot Trial

With the aim to pilot a full-scaled trial to reduce unnecessary antibiotics in women with suspected uncomplicated urinary tract infections, twenty general practices in Bavaria, Germany, will be randomized to deliver patient management based on phase-contrast microscopy and urinary dipsticks or to usual care. Primary endpoints are recruitment and retention rates.

Study Overview

• Status: Completed
• Conditions: Medication Adherence; Antibiotic Resistant Infection; Urinary Tract Infection Lower Acute; Urinary Tract Infection Bacterial; Cystitis Acute
• Intervention / Treatment: Diagnostic test: Point-of-care microscopy and dipstick guided management

Detailed Description

Introduction: Uncomplicated urinary tract infections (UTIs) in women are among the most common infections encountered in primary care after those of the respiratory tract. They are often self-limiting, even though antibiotics are prescribed for almost all women presenting with suggestive clinical features. Efforts directed to tackle antimicrobial resistance led to primary care randomized controlled trials (RCTs) that investigated alternative treatment strategies in these patients. While reducing antibiotic use substantially, none of the experimental treatments showed non-inferiority to antibiotics with respect to clinical outcomes such as symptom duration, symptom burden, and pyelonephritis. Evidence suggests that rapid point-of-care (POC) tests to detect bacteria and erythrocytes in urine at presentation may help primary care clinicians to select women with uncomplicated UTIs (unUTIs) in whom antibiotics can be withheld without affecting clinical outcomes. The aim of this study is to pilot a full-scaled primary care RCT to evaluate the effects of a POC diagnosis and treatment algorithm based on a combination of phase-contrast microscopy and urinary dipsticks on antibiotic use in women with symptoms of an unUTI.

Methods and analysis: MicUTI (Microscopy in UTI) is a pragmatic open-label two -arm parallel pilot cluster-RCT. Twenty general practices affiliated to the Bavarian Practice Based Research Network (BayFoNet) in Germany will be randomly assigned to deliver patient management based on POC-tests (POCTs) or to the usual care arm. Urine samples will be obtained at presentation for POCTs and microbiological analysis. All patients will be followed-up using a self-directed patient diary completed until day 7 from inclusion or until symptom resolution (up to day 14), and through telephone-calls at day 28. An electronic medical record review is performed in case of missing follow-up information.

Primary endpoints are patient enrollment and retention rates. Exploratory endpoints include antibiotic use for UTI at day 28, time to symptom resolution, symptom burden, the number of recurrent and upper UTIs and re-consultations, and diagnostic accuracy (POCTs vs. urine culture as reference standard).

Ethics, data protection and trial registration: The trial will be conducted in accordance to the declaration of Helsinki and the relevant data protection regulations. Institutional review board approval: 109/22-sc (December 16, 2022)

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Stefanie Stark
  • Würzburg, Germany, 97080
    • University Hospital Wurzburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with at least two of dysuria, frequency, urgency, lower abdominal pain or hematuria.

Exclusion Criteria:

• Signs of a complicated UTI (anamnesis of fever, chills or flank pain)
• Clinically relevant immunosuppression (i.e., current use of any immunosup-pressive therapy, congenital or acquired disorders of immunity)
• Acute or chronic functional or anatomical variations in urinary tract except renal insufficiency grade II/IIIa
• Permanent bladder catheter or use of bladder catheter within the past two weeks
• UTI within the past two weeks
• Use of any antibiotic within the past two weeks
• Accommodation in a nursing home or hospital stay within the past two weeks
• Severe neurologic or psychiatric illness, severe dementia or severe substance use disorder
• Other severe diseases
• Being unable to understand the informed consent or to complete the patient diary
• Known pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Point-of-care microscopy and dipstick guided management; GPs whose practice is allocated to the intervention will have their management guided by POCTs, namely phase-contrast microscopy and urinary dipsticks for all patients consenting for participation.	Diagnostic test: Point-of-care microscopy and dipstick guided management; GPs will be encouraged to apply the following diagnosis and treatment algorithm (figure 1) to consenting women, taking their preferences into account: If POCTs are positive for bacteria by microscopy and/or for erythrocytes by dipsticks the GP issues, at his/her own clinical judgement, a delayed or immediate prescription for an antibiotic.10 In the MicUTI intervention, delayed prescription is defined as issuing an antibiotic prescription with the advice to take the medication only when symptoms do not improve or worsen in 48 hours.; If POCTs are negative for bacteria and erythrocytes, the GP advises for self-help remedies according to guidelines and to do without antibiotics Study specific training in point-of-care microscopy will be provided to intervention practices.
No Intervention: Usual care; Practices in the control arm will not have their management guided by POCTs. They will perform usual care. The treatment decision is usually based on symptoms and dip-stick test results (i.e., erythrocytes, leukocytes, nitrites).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment efficacy	Number of participants enrolled per site over 6 months of trial duration	6 months (duration of the trial in each study site)
Retention	Percentage of complete follow-ups over 28 days	28 days (duration of the trial for each enrolled patient)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total antibiotic use	Number of antibiotic prescriptions per patient with UTI within 28 days	28 days
Antibiotic doses	Defined daily doses of the prescribed antibiotics per patient with UTI within 28 days	28 days
Inappropriate antibiotic use	Percentage of patients with symptoms of UTI who were prescribed antibiotics among those with negative urine cultures	Day 0
Immediate and delayed antibiotics	Number of immediate and delayed antibiotic prescriptions for uncomplicated UTI at initial consultation	Day 0
Early relapses	Number of early relapses of UTI (days 0-14)	Days 0-14
Recurrent urinary tract infections (UTIs)	Number of recurrent UTIs (day 15-28)	Days 15-28
Upper UTIs	Number of upper UTIs within 28 days	28 days
Re-consultations	Number of consultations due to UTI (or symptoms of UTI) within 28 days	28 days
Symptom resolution	Time to symptom resolution defined as a maximum of 1 point in each of the UTI-SIQ-8 items	Days 0-7 (or max. 14 if symptoms last longer)
Symptom Burden	Total symptom burden on days 0-7 (area under the curve of the UTI-SIQ-8 total symptom score)	Days 0-14
Diagnostic accuracy	Diagnostic accuracy of microscopy +/- dipstick compared to the standard (urine culture)	Day 0

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: University of Bristol; University of Georgia; LMU Klinikum; University of Wuerzburg; University of Santiago de Compostela; University Hospital Erlangen; Università degli Studi di Trento
• Investigators: Principal Investigator: Ildikó Gágyor, Professor, University Hospital Wuerzburg

Publications and helpful links

General Publications

• Kurotschka PK, Borgulya G, Bucher E, Endrich I, Figueiras A, Gensichen J, Hay AD, Hapfelmeier A, Kretzschmann C, Kurzai O, Lam TT, Massidda O, Sanftenberg L, Schmiemann G, Schneider A, Simmenroth A, Stark S, Warkentin L, Ebell MH, Gagyor I; Bavarian Practice-Based Research Network (BayFoNet). Dipsticks and point-of-care Microscopy to reduce antibiotic use in women with an uncomplicated Urinary Tract Infection (MicUTI): protocol of a randomised controlled pilot trial in primary care. BMJ Open. 2024 Mar 29;14(3):e079345. doi: 10.1136/bmjopen-2023-079345.

Helpful Links

• Study Protocol

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: randomized controlled trial; Primary care; feasibility; pilot study; General Practice; randomized clinical trial; cluster-randomized trial; point-of-care test; microscopy; urinary dipsticks; clinical decision algorithm
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Disease Attributes; Bacterial Infections and Mycoses; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis; Infections; Communicable Diseases; Urinary Tract Infections; Bacterial Infections
• Other Study ID Numbers: 109/22-sc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No