title: Treatment duration of febrile urinary tract infection: a pragmatic randomized, double-blind, placebo-controlled non-inferiority trial in men and women.
abstract: BACKGROUND
  In adults with febrile urinary tract infection (fUTI), data on optimal treatment duration in patients other than non-pregnant women without comorbidities are lacking.
  
  
  METHODS
  A randomized placebo-controlled, double-blind, non-inferiority trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥ 18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days (the second week being ciprofloxacin 500 mg or placebo orally twice daily). Patients indicated to receive antimicrobial treatment for at least 14 days were excluded from randomization. The primary endpoint was the clinical cure rate through the 10- to 18-day post-treatment visit with preset subgroup analysis including sex. Secondary endpoints were bacteriologic cure rate at 10-18 days post-treatment and clinical cure at 70-84 days post-treatment.
  
  
  RESULTS
  Of 357 patients included, 200 were eligible for randomization; 97 patients were randomly assigned to 7 days and 103 patients to 14 days of treatment. Overall, short-term clinical cure occurred in 85 (90%) patients treated for 7 days and in 94 (95%) of those treated for 14 days (difference -4.5%; 90% CI, -10.7 to 1.7; Pnon-inferiority= 0.072, non-inferiority not confirmed). In women, clinical cure was 94% and 93% in those treated for 7 and 14 days, respectively (difference 0.9; 90% CI, -6.9 to 8.7, Pnon-inferiority= 0.011, non-inferiority confirmed) and, in men, this was 86% versus 98% (difference -11.2; 90% CI -20.6 to -1.8, Psuperiority= 0.025, inferiority confirmed). The bacteriologic cure rate was 93% versus 97% (difference -4.3%; 90% CI, -9.7 to 1.2, Pnon-inferiority= 0.041) and the long-term clinical cure rate was 92% versus 91% (difference 1.6%; 90% CI, -5.3 to 8.4; Pnon-inferiority= 0.005) for 7 days versus 14 days of treatment, respectively. In the subgroups of men and women, long-term clinical cure rates met the criteria for non-inferiority, indicating there was no difference in the need for antibiotic retreatment for UTI during 70-84 days follow-up post-treatment.
  
  
  CONCLUSIONS
  Women with fUTI can be treated successfully with antibiotics for 7 days. In men, 7 days of antibiotic treatment for fUTI is inferior to 14 days during short-term follow-up but it is non-inferior when looking at longer follow-up.
  
  
  BACKGROUND
  The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].
authors.affiliation: Department of Internal Medicine, Haga Teaching Hospital, Els-Borst Eilersplein 245, 2545 AA, The Hague, The Netherlands. c.vannieuwkoop@hagaziekenhuis.nl.|Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. c.vannieuwkoop@hagaziekenhuis.nl.
authors.forename: Cees
authors.identifier: http://orcid.org/0000-0003-0734-0844
authors.initials: C
authors.lastname: van Nieuwkoop
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Willize E
authors.initials: WE
authors.lastname: van der Starre
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Janneke E
authors.initials: JE
authors.lastname: Stalenhoef
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: van Aartrijk
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tanny J K
authors.initials: TJ
authors.lastname: van der Reijden
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Vollaard
authors.affiliation: Department of Internal Medicine, Alrijne Hospital, Leiderdorp, The Netherlands.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delfos
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.|Department of Internal Medicine, Bronovo Hospital, The Hague, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: van 't Wout
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeanet W
authors.initials: JW
authors.lastname: Blom
authors.affiliation: Primary Health Care Center, Wassenaar, The Netherlands.
authors.forename: Ida C
authors.initials: IC
authors.lastname: Spelt
authors.affiliation: Department of Internal Medicine, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Eliane M S
authors.initials: EM
authors.lastname: Leyten
authors.affiliation: Department of Internal Medicine, Groene Hart Hospital, Gouda, The Netherlands.
authors.forename: Ted
authors.initials: T
authors.lastname: Koster
authors.affiliation: Department of Internal Medicine, Alrijne Hospital, Leiden, The Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Ablij
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martha T
authors.initials: MT
authors.lastname: van der Beek
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control (CIb), Bilthoven, The Netherlands.
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: Knol
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.|National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control (CIb), Bilthoven, The Netherlands.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010919:Placebos; D013997:Time Factors; D014552:Urinary Tract Infections / Q000150:complications / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D010919:Placebos; D002939:Ciprofloxacin
keywords: Antibiotic therapy; Pyelonephritis; Treatment duration; Urinary tract infection