title: Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.
abstract: BACKGROUND
  Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.
  
  
  METHODS
  In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.
  
  
  RESULTS
  Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).
  
  
  CONCLUSIONS
  A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.
  
  
  BACKGROUND
  Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.
authors.affiliation: Service de Réanimation Médicale, Université Paris 7-Denis-Diderot, Hôpital Bichat-Claude-Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Bouadma
authors.forename: Charles-Edouard
authors.initials: CE
authors.lastname: Luyt
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.forename: Christophe
authors.initials: C
authors.lastname: Cracco
authors.forename: Antonio
authors.initials: A
authors.lastname: Alvarez
authors.forename: Carole
authors.initials: C
authors.lastname: Schwebel
authors.forename: Frédérique
authors.initials: F
authors.lastname: Schortgen
authors.forename: Sigismond
authors.initials: S
authors.lastname: Lasocki
authors.forename: Benoît
authors.initials: B
authors.lastname: Veber
authors.forename: Monique
authors.initials: M
authors.lastname: Dehoux
authors.forename: Maguy
authors.initials: M
authors.lastname: Bernard
authors.forename: Blandine
authors.initials: B
authors.lastname: Pasquet
authors.forename: Bernard
authors.initials: B
authors.lastname: Régnier
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.forename: Jean
authors.initials: J
authors.lastname: Chastre
authors.forename: Michel
authors.initials: M
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D016638:Critical Illness; D003661:Decision Support Techniques; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data*; D024881:Drug Resistance, Bacterial; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide