title: Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing.
abstract: BACKGROUND
  The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs.
  
  
  METHODS
  A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost.
  
  
  RESULTS
  Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost.
  
  
  CONCLUSIONS
  rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation.
  
  
  BACKGROUND
  NCT01898208.
authors.affiliation: Division of Pediatric Infectious Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ritu
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Department of Pharmacy, National University of Singapore and Tan Tock Seng Hospital, Singapore.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Teng
authors.affiliation: Division of Laboratory Medicine and Pathology.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Cunningham
authors.affiliation: Division of Laboratory Medicine and Pathology.
authors.forename: Sherry M
authors.initials: SM
authors.lastname: Ihde
authors.affiliation: Division of Infectious Diseases.
authors.forename: James M
authors.initials: JM
authors.lastname: Steckelberg
authors.affiliation: Division of Health Care Policy and Research.
authors.forename: James P
authors.initials: JP
authors.lastname: Moriarty
authors.affiliation: Division of Health Care Policy and Research.
authors.forename: Nilay D
authors.initials: ND
authors.lastname: Shah
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jayawant N
authors.initials: JN
authors.lastname: Mandrekar
authors.affiliation: Division of Laboratory Medicine and Pathology Division of Infectious Diseases.
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058889:Molecular Typing; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents
keywords: PCR; antimicrobial stewardship; blood culture; diagnostic