title: Procalcitonin, pyuria and proadrenomedullin in the management of urinary tract infections--'triple p in uti': study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Urinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions.
  
  
  METHODS
  This randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent. For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines. The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions.
  
  
  CONCLUSIONS
  This trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability.
  
  
  BACKGROUND
  
  
  
  BACKGROUND
  ISRCTN13663741.
authors.affiliation: Medical University Department, University of Basel, Kantonsspital Aarau, Tellstrasse, Aarau 5001, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Drozdov
authors.forename: Anja
authors.initials: A
authors.lastname: Thomer
authors.forename: Marc
authors.initials: M
authors.lastname: Meili
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schwarz
authors.forename: Rita Bossart
authors.initials: RB
authors.lastname: Kouegbe
authors.forename: Katharina
authors.initials: K
authors.lastname: Regez
authors.forename: Merih
authors.initials: M
authors.lastname: Guglielmetti
authors.forename: Ursula
authors.initials: U
authors.lastname: Schild
authors.forename: Antoinette
authors.initials: A
authors.lastname: Conca
authors.forename: Petra
authors.initials: P
authors.lastname: Schäfer
authors.forename: Barbara
authors.initials: B
authors.lastname: Reutlinger
authors.forename: Cornelia
authors.initials: C
authors.lastname: Ottiger
authors.forename: Florian
authors.initials: F
authors.lastname: Buchkremer
authors.forename: Alexander
authors.initials: A
authors.lastname: Litke
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bürgi
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Andreas
authors.initials: A
authors.lastname: Bock
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Werner C
authors.initials: WC
authors.lastname: Albrich
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002985:Clinical Protocols; D004636:Emergency Service, Hospital; D019983:Guideline Adherence; D006801:Humans; D007902:Length of Stay; D010343:Patient Admission; D010351:Patient Discharge; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D012107:Research Design; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D014218:Triage; D014552:Urinary Tract Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide