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, Eleftherios; Clancy, Cornelius J.; Ostrosky-Zeichner, Luis; Garey, Kevin W.; Alangaden, George J.; Vazquez, Jose A.; Groeger, Jeffrey S.; Judson, Marc A.; Vinagre, Yuka-Marie; Heard, Stephen O.; Zervou, Fainareti N.; Zacharioudakis, Ioannis M.; Kontoyiannis, Dimitrios P.; and Pappas, Peter G., "T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial" (2015). Anesthesiology and Perioperative Medicine Publications. 176.