T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial
Department of Anesthesiology
Adult; Aged; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidemia; Female; Humans; Limit of Detection; Magnetic Resonance Spectroscopy; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity
Anesthesiology | Infectious Disease
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.
CLINICAL TRIALS REGISTRATION: NCT01752166.
DOI of Published Version
Clin Infect Dis. 2015 Mar 15;60(6):892-9. doi: 10.1093/cid/ciu959. Epub 2015 Jan 12. Link to article on publisher's site
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, Groeger JS, Judson MA, Vinagre Y, Heard SO, Zervou FN, Zacharioudakis IM, Kontoyiannis DP, Pappas PG. (2015). T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Anesthesiology and Perioperative Medicine Publications. https://doi.org/10.1093/cid/ciu959. Retrieved from https://escholarship.umassmed.edu/anesthesiology_pubs/176