TY - JOUR
T1 - T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood
T2 - A clinical trial
AU - Mylonakis, Eleftherios
AU - Clancy, Cornelius J.
AU - Ostrosky-Zeichner, Luis
AU - Garey, Kevin W.
AU - Alangaden, George J.
AU - Vazquez, Jose A.
AU - Groeger, Jeffrey S.
AU - Judson, Marc A.
AU - Vinagre, Yuka Marie
AU - Heard, Stephen O.
AU - Zervou, Fainareti N.
AU - Zacharioudakis, Ioannis M.
AU - Kontoyiannis, Dimitrios P.
AU - Pappas, Peter G.
N1 - Funding Information:
Acknowledgments. The authors acknowledge Drs Robert Langer and Tom Lowery for helpful discussions. Financial support. This work was supported by T2 Biosystems.
PY - 2015/3/15
Y1 - 2015/3/15
N2 - 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 colonyforming 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.
AB - 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 colonyforming 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.
KW - Candida
KW - Clinical trial
KW - Fungal infections
KW - T2 magnetic resonance
KW - T2MR
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U2 - 10.1093/cid/ciu959
DO - 10.1093/cid/ciu959
M3 - Article
C2 - 25586686
AN - SCOPUS:84929863300
SN - 1058-4838
VL - 60
SP - 892
EP - 899
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 6
ER -