title: Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial.
abstract: BACKGROUND
  The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined.
  
  
  OBJECTIVE
  To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality.
  
  
  METHODS
  This was a multicenter (11 Australian intensive care units [ICUs]), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28.
  
  
  RESULTS
  PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio [95% confidence interval], 2.76 [1.10-6.96], P = 0.03; 3.20 [1.30-7.89], P = 0.01, respectively).
  
  
  CONCLUSIONS
  In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).
authors.affiliation: 1 University of New South Wales Clinical School, Randwick, Australia.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Shehabi
authors.forename: Martin
authors.initials: M
authors.lastname: Sterba
authors.forename: Peter Maxwell
authors.initials: PM
authors.lastname: Garrett
authors.forename: Kanaka Sundaram
authors.initials: KS
authors.lastname: Rachakonda
authors.forename: Dianne
authors.initials: D
authors.lastname: Stephens
authors.forename: Peter
authors.initials: P
authors.lastname: Harrigan
authors.forename: Alison
authors.initials: A
authors.lastname: Walker
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Millis
authors.forename: Geoff
authors.initials: G
authors.lastname: Ding
authors.forename: Sandra
authors.initials: S
authors.lastname: Peake
authors.forename: Helen
authors.initials: H
authors.lastname: Wong
authors.forename: Jane
authors.initials: J
authors.lastname: Thomas
authors.forename: Kate
authors.initials: K
authors.lastname: Smith
authors.forename: Loretta
authors.initials: L
authors.lastname: Forbes
authors.forename: Miranda
authors.initials: M
authors.lastname: Hardie
authors.forename: Sharon
authors.initials: S
authors.lastname: Micallef
authors.forename: John F
authors.initials: JF
authors.lastname: Fraser
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001315:Australia; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D003422:Critical Care; D016638:Critical Illness; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D016037:Single-Blind Method
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
keywords: critically ill; infection; intensive care; procalcitonin; sepsis