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Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis

  • Applied microbial and cell physiology
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Abstract

Early and accurate diagnosis of invasive aspergillosis (IA) is one of the most critical steps needed to efficiently treat the infection and reduce the high mortality rates that can occur. We have previously found that the Aspergillus spp. secondary metabolite, bis(methylthio)gliotoxin (bmGT), can be detected in the serum from patients with possible/probable IA. Thus, it could be used as a diagnosis marker of the infection. However, there is no data available concerning the sensitivity, specificity and performance of bmGT to detect the infection. Here, we have performed a prospective study comparing bmGT detection with galactomannan (GM), the most frequently used and adopted approach for IA diagnosis, in 357 sera from 90 episodes of patients at risk of IA. Our results, involving 79 patients that finally met inclusion criteria, suggest that bmGT presents higher sensitivity and positive predictive value (PPV) than GM and similar specificity and negative predictive value (NPV). Importantly, the combination of GM and bmGT increased the PPV (100 %) and NPV (97.5 %) of the individual biomarkers, demonstrating its potential utility in empirical antifungal treatment guidance and withdrawal. These results indicate that bmGT could be a good biomarker candidate for IA diagnosis and, in combination with GM, could result in highly specific diagnosis of IA and management of patients at risk of infection.

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Authors and Affiliations

  1. Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain

    Matxalen Vidal-García, Lourdes Roc, M. José Revillo & Antonio Rezusta

  2. Instituto de Carboquímica, ICB-CSIC, Zaragoza, Spain

    M. Pilar Domingo & Eva M. Gálvez

  3. Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain

    Beatriz De Rueda & M. Pilar Delgado

  4. Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain

    Julián Pardo & Antonio Rezusta

  5. Centro de Investigación Biomédica de Aragón (CIBA), Zaragoza, Spain

    Julián Pardo

  6. Aragon I+D Foundation, Zaragoza, Spain

    Julián Pardo

  7. University of Zaragoza, Zaragoza, Spain

    Julián Pardo & Antonio Rezusta

Authors
  1. Matxalen Vidal-García
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  2. M. Pilar Domingo
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  3. Beatriz De Rueda
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  4. Lourdes Roc
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  5. M. Pilar Delgado
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  6. M. José Revillo
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  7. Julián Pardo
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  8. Eva M. Gálvez
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  9. Antonio Rezusta
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Corresponding author

Correspondence to Matxalen Vidal-García.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the local ethics committee CEICA (PI12/0041 and PI15/0197).

Funding

This work has been supported by Fondo Social Europeo (FSE/Gobierno de Aragón) and ARAID Foundation (J.P.)

Conflict of interest

M.P. Domingo, J. Pardo and E.M. Gálvez are co-inventors of a patent licensed to Blackhills Diagnostics Resources S.L. that protects the use of bmGT to diagnose IA (PCT/EP2012/058,247). All the other authors declare that they have no competing interests.

Additional information

Eva M. Gálvez and Antonio Rezusta contributed equally to this manuscript.

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Vidal-García, M., Domingo, M.P., De Rueda, B. et al. Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis. Appl Microbiol Biotechnol 100, 2327–2334 (2016). https://doi.org/10.1007/s00253-015-7209-6

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  • DOI: https://doi.org/10.1007/s00253-015-7209-6

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