title: T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial.
abstract: BACKGROUND
  Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia.
  
  
  METHODS
  Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species.
  
  
  RESULTS
  T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively.
  
  
  CONCLUSIONS
  T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics.
  
  
  BACKGROUND
  NCT01752166.
authors.affiliation: Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.affiliation: Veterans Affairs Pittsburgh Healthcare System, Division of Infectious Diseases, University of Pittsburgh, Pennsylvania.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: Division of Infectious Diseases, University of Texas Medical School at Houston and Memorial Hermann Texas Medical Center.
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.affiliation: University of Houston College of Pharmacy, Texas.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Garey
authors.affiliation: Division of Infectious Diseases, Henry Ford Health System, Detroit, Michigan.
authors.forename: George J
authors.initials: GJ
authors.lastname: Alangaden
authors.affiliation: Department of Medicine, Medical College of Georgia at Georgia Regents University, Augusta.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Vazquez
authors.affiliation: Urgent Care Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Groeger
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Albany Medical College, New York.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Judson
authors.affiliation: Department of Critical Care Medicine, St Vincent Hospital.
authors.forename: Yuka-Marie
authors.initials: YM
authors.lastname: Vinagre
authors.affiliation: Department of Anesthesiology, UMass Memorial Medical Center, Worcester, Massachusetts.
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Heard
authors.affiliation: Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence.
authors.forename: Fainareti N
authors.initials: FN
authors.lastname: Zervou
authors.affiliation: Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence.
authors.forename: Ioannis M
authors.initials: IM
authors.lastname: Zacharioudakis
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Pappas
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents; D002175:Candida / Q000302:isolation & purification*; D002176:Candida albicans / Q000302:isolation & purification; D041221:Candida glabrata / Q000302:isolation & purification; D041022:Candida tropicalis / Q000302:isolation & purification; D058387:Candidemia / Q000175:diagnosis*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000935:Antifungal Agents
keywords: Candida; T2 magnetic resonance; T2MR; clinical trial; fungal infections