T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood

A clinical trial

Eleftherios Mylonakis, Cornelius J. Clancy, Luis Ostrosky-Zeichner, Kevin W. Garey, George J. Alangaden, Jose Antonio Vazquez, Jeffrey S. Groeger, Marc A. Judson, Yuka Marie Vinagre, Stephen O. Heard, Fainareti N. Zervou, Ioannis M. Zacharioudakis, Dimitrios P. Kontoyiannis, Peter G. Pappas

Research output: Contribution to journalArticle

175 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)892-899
Number of pages8
JournalClinical Infectious Diseases
Volume60
Issue number6
DOIs
StatePublished - Jan 1 2015

Fingerprint

Candidemia
Magnetic Resonance Spectroscopy
Clinical Trials
Confidence Intervals
Candida
Candida tropicalis
Candida glabrata
Candida albicans
Molecular Pathology
Standard of Care
Multicenter Studies
Limit of Detection
Technology

Keywords

  • Candida
  • Clinical trial
  • Fungal infections
  • T2 magnetic resonance
  • T2MR

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Mylonakis, E., Clancy, C. J., Ostrosky-Zeichner, L., Garey, K. W., Alangaden, G. J., Vazquez, J. A., ... Pappas, P. G. (2015). T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: A clinical trial. Clinical Infectious Diseases, 60(6), 892-899. https://doi.org/10.1093/cid/ciu959

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

In: Clinical Infectious Diseases, Vol. 60, No. 6, 01.01.2015, p. 892-899.

Research output: Contribution to journalArticle

Mylonakis, E, Clancy, CJ, Ostrosky-Zeichner, L, Garey, KW, Alangaden, GJ, Vazquez, JA, Groeger, JS, Judson, MA, Vinagre, YM, 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', Clinical Infectious Diseases, vol. 60, no. 6, pp. 892-899. https://doi.org/10.1093/cid/ciu959
Mylonakis, Eleftherios ; Clancy, Cornelius J. ; Ostrosky-Zeichner, Luis ; Garey, Kevin W. ; Alangaden, George J. ; Vazquez, Jose Antonio ; Groeger, Jeffrey S. ; Judson, Marc A. ; Vinagre, Yuka Marie ; Heard, Stephen O. ; Zervou, Fainareti N. ; Zacharioudakis, Ioannis M. ; Kontoyiannis, Dimitrios P. ; Pappas, Peter G. / T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood : A clinical trial. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 6. pp. 892-899.
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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 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.",
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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 Antonio

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.

PY - 2015/1/1

Y1 - 2015/1/1

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.

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KW - Clinical trial

KW - Fungal infections

KW - T2 magnetic resonance

KW - T2MR

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