title: Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial.
abstract: OBJECTIVE
  Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen. We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis.
  
  
  METHODS
  This multicentre, randomised, controlled, single-blind trial was performed in two parallel groups.
  
  
  METHODS
  Eight intensive care units in France.
  
  
  METHODS
  Adults with the phenotype of severe sepsis and no overt source of infection, negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission.
  
  
  METHODS
  The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians' clinical judgement without reference to procalcitonin values in the control arm.
  
  
  METHODS
  The primary outcome was the proportion of patients on antibiotics on day 5 postrandomisation.
  
  
  RESULTS
  Over a 3-year period, 62/1250 screened patients were eligible for the study, of whom 31 were randomised to each arm; 4 later withdrew their consent. At day 5, 18/27 (67%) survivors were on antibiotics in the experimental arm, versus 21/26 (81%) controls (p=0.24; relative risk=0.83, 95% CI: 0.60 to 1.14). Only 8/58 patients (13%) had baseline procalcitonin <0.25 µg/l; in these patients, physician complied poorly with the algorithm.
  
  
  CONCLUSIONS
  In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen, the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure. However, the premature termination of the trial may not allow definitive conclusions.
authors: Service de Reanimation, Hôpital Raymond Poincaré (AP-HP),  University of Versailles SQY 104 boulevard Raymond Poincaré, 92380, Garches,  France.
authors: Djillali
authors: D
authors: Annane
authors: Virginie
authors: V
authors: Maxime
authors: Jean Pierre
authors: JP
authors: Faller
authors: Chaouki
authors: C
authors: Mezher
authors: Christophe
authors: C
authors: Clec'h
authors: Patricia
authors: P
authors: Martel
authors: Hélène
authors: H
authors: Gonzales
authors: Marc
authors: M
authors: Feissel
authors: Yves
authors: Y
authors: Cohen
authors: Gilles
authors: G
authors: Capellier
authors: Miloud
authors: M
authors: Gharbi
authors: Olivier
authors: O
authors: Nardi