Febrile Urinary Tract Infection Randomized Short Treatment Trial (FUTIRST)

Relevance of Biomarkers and Clinical Predictors of Outcome in Unselected Population With Febrile Urinary Tract Infection at Primary Care and Emergency Department in a Prospective, Randomized Cohort Trial Comparing Short (7 Days) Antibiotic Treatment With Conventional Treatment (14 Days)

Bronovo Hospital, Medical Center Haaglanden, Spaarne Gasthuis, Rijnland Hospital, Diaconessenhuis Leiden, Groene Hart Ziekenhuis

The purpose of this study is to determine whether a 7-day duration of antibiotic treatment of febrile urinary tract infection (FUTI) is non inferior to 14-day standard duration of treatment in unselected population presenting at primary care or emergency department.

In the last decades hospitalization rates of patients with acute pyelonephritis (AP) or FUTI has decreased from almost 100% to 10-30%. The outpatient management of patients with FUTI has become popular as well as oral antimicrobial treatment regiments and shortening of treatment duration. However, as such approaches are only discovered in otherwise young health non-pregnant women, the best management of FUTI in the elderly, men and patients with co-morbidity remains elusive. Bases on personal perception of the attending physician antibiotic treatment, duration varies approximately between 7-14 days. Facing the aging of the general population, it is urgent to better define the optimal treatment for AP or FUTI in an unselected population and to identify those at risk for treatment failure or poor outcome to guide and optimize individual patient management and to prevent on the one hand unnecessary long treatment duration and hospital admission and on the other hand unsafe short duration or unsafe outpatient management. In this study the efficacy and safety of a 7-day antimicrobial regimen compared to a 14-day antimicrobial regimen will be evaluated in an unselected population presenting with FUTI at primary care or emergency department. In addition a clinical and/or biomarker based scoring system of disease severity will be derived to predict those at risk for treatment failure or poor outcome.

Urinary Tract Infection, Fever, Acute Pyelonephritis, Treatment duration, Febrile Urinary Tract Infection Treatment Duration

14 days of standard antibiotic treatment (initial b-lactam or fluoroquinolone followed by ciprofloxacin through the 8th till 14th day)

7 days of antibiotic treatment for febrile urinary tract infection / acute pyelonephritis compared to standard treatment of 14 days

Clinical cure rate through the 10- to 18-day posttherapy visit. Clinical cure is defined as the resolution of fever and signs and symptoms of UTI.

Inclusion Criteria: Competent patient aged 18 years or above One or more symptom(s) suggestive of urinary tract infection (dysuria, frequency or urgency*; perineal or suprapubic pain; costo-vertebral tenderness or flank pain) Fever (ear or rectal temp of 38.2 oC or higher, or axillary temp of 38 oC or higher), or history of feeling feverish with shivering or rigors in the past 24 hours Positive urine nitrate test and/or leucocyturia as depicted by positive leukocyte esterase test or microscopy Exclusion Criteria: Known allergy to fluoroquinolones Female patients who are pregnant or lactating Patients with known polycystic kidney disease Patients on permanent renal replacement therapy (hemodialysis or peritoneal dialysis) Patients with history of kidney transplantation Residence outside country of enrolment Inability to speak or read Dutch Isolated causal uropathogen resistant to ciprofloxacin Renal abscess Chronic bacterial prostatitis Suspicion or evidence of any metastatic infectious foci

van Nieuwkoop C, van't Wout JW, Assendelft WJ, Elzevier HW, Leyten EM, Koster T, Wattel-Louis GH, Delfos NM, Ablij HC, Kuijper EJ, Pander J, Blom JW, Spelt IC, van Dissel JT. Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days). BMC Infect Dis. 2009 Aug 19;9:131. doi: 10.1186/1471-2334-9-131.

Stalenhoef JE, van Nieuwkoop C, Wilson DC, van der Starre WE, van der Reijden TJK, Delfos NM, Leyten EMS, Koster T, Ablij HC, van 't Wout JJW, van Dissel JT. Procalcitonin, mid-regional proadrenomedullin and C-reactive protein in predicting treatment outcome in community-acquired febrile urinary tract infection. BMC Infect Dis. 2019 Feb 14;19(1):161. doi: 10.1186/s12879-019-3789-6.

van Nieuwkoop C, van der Starre WE, Stalenhoef JE, van Aartrijk AM, van der Reijden TJ, Vollaard AM, Delfos NM, van 't Wout JW, Blom JW, Spelt IC, Leyten EM, Koster T, Ablij HC, van der Beek MT, Knol MJ, van Dissel JT. Treatment duration of febrile urinary tract infection: a pragmatic randomized, double-blind, placebo-controlled non-inferiority trial in men and women. BMC Med. 2017 Apr 3;15(1):70. doi: 10.1186/s12916-017-0835-3.