Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting.
Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting.
We propose to perform a randomized controlled patient and assessor blind trial in women
 between the ages of 18 to 70 years with acute uncomplicated UTI to evaluate initial
 symptomatic treatment for 3 days with the non-steroidal anti-inflammatory drug diclofenac
 (experimental intervention) against immediate antibiotic treatment with norfloxacin for 3
 days (control intervention). Both interventions are followed by optional delayed antibiotic
 treatment with single dose fosfomycin if deemed necessary by the patients. The primary
 objective is to determine whether initial symptomatic treatment followed by optional delayed
 antibiotic treatment (experimental intervention) is non-inferior to immediate antibiotic
 treatment (control intervention) in terms of symptom resolution.
Background

 Urinary tract infection (UTI) is the most frequent bacterial infection diagnosed and treated
 by general practitioners and accounts for about 15% of antibiotic prescriptions in ambulatory
 medicine. World-wide raise of antibiotic resistance among uropathogens, most commonly
 Escherichia coli, threatens treatment of UTI. Uncomplicated UTI, the most frequent
 manifestation of UTI, is a benign, self-limited disease and the primary goal of treatment is
 symptom relief not cure. Antibiotic treatment reduces the duration of symptoms by 1-2 days
 from 5-6 days to 3-4 days. Symptoms of cystitis are the result of an inflammation evoked by
 bacterial products which stimulate the production of prostaglandins by a cyclooxygenase
 dependent mechanism. Therefore, we propose that symptom control with a non-steroidal
 anti-inflammatory drug (NSAID), an inhibitor of cyclooxygenase 1 and 2, may be equally
 effective for symptom control as standard antibiotic therapy in non-complicated UTI and may
 therefore help to reduce antibiotic consumption.

 Objective

 The primary objective is to determine whether initial symptomatic treatment followed by
 optional delayed antibiotic treatment (experimental intervention) is non-inferior to
 immediate antibiotic treatment followed by optional delayed antibiotic treatment (control
 intervention) in terms of symptom resolution.

 The secondary objective is to determine whether the experimental intervention is superior to
 control in reducing the proportion of patients undergoing antibiotic treatment.

 Methods

 Randomized controlled patient and assessor blind trial performed in general practices. Study
 population are women between the ages of 18 to 70 years with acute uncomplicated UTI. The
 experimental intervention will consist of symptomatic treatment with diclofenac 75mg twice
 daily, followed by optional, delayed antibiotic treatment with single dose of 3g fosfomycin
 if deemed necessary by the patient. The control intervention will consist of immediate
 antibiotic treatment with norfloxacin 400mg twice daily for three days, followed by optional,
 delayed antibiotic treatment with single dose of 3g fosfomycin if deemed necessary by the
 patient. Patients will use a diary to describe symptoms for 10 days. A follow-up telephone
 interview will be performed on day 10 and 30.
Inclusion Criteria:

 -  Female

 -  Age between 18 and 70 years

 -  Written informed consent

 -  At least one typical symptom of acute, lower urinary tract infection out of dysuria,
 frequency, macrohaematuria, cloudy or smelly urine or self-diagnosed cystitis

 -  A urine dipstick test should be indicative of UTI by positive nitrite or leucocyturia

 Exclusion Criteria

 -  Duration of UTI symptoms for more than 7 days before physician's visit

 -  Clinical signs of invasiveness such as fever (axillary body temperature >38 degrees
 Celsius), costovertebral pain or tenderness, rigors, nausea or vomiting

 -  Known or suspicion of anatomical or functional abnormality of the urinary tract

 -  Vaginal symptoms: discharge, irritation

 -  Diabetes mellitus

 -  Immunosuppression (e.g. prednisone equivalent >10mg per day for >14 days,
 chemotherapy, radiotherapy, immunomodulators, HIV infection, neutropenia)

 -  Any other serious comorbidity as judged by the treating physician

 -  Bladder catheter in situ or during the past 30 days

 -  Pregnancy

 -  Recurrent urinary tract infection (more than 3 infections during the last 12 months)

 -  Antibiotic treatment during the last 4 weeks

 -  Hypersensitivity to one of the study medications

 -  Psychiatric illness or dementia

 -  Unable to communicate in German or French language

 -  Documented coagulopathy (including therapy with coumarine derivatives) or documented
 history of gastric or duodenal ulcer disease

 -  Documented renal insufficiency grade III or higher (calculated GFR <60) or known
 congestive heart failure (NYHA III or higher)