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Heteroresistance to Fluconazol in Clinical and Environmental Brazilian Strains of Cryptococcus neoformans/C. gattii Species Complex

  • Clinical Mycology Lab Issues (S Córdoba, Section Editor)
  • Published:
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Abstract

Purpose of Study

To review the literature on heteroresistance to fluconazole (FLC) and investigate the level of heteroresistance to FLC (LHF), we analyzed 100 clinical and environmental Brazilian Cryptococcus strains.

Recent Findings

Heteroresistance is a phenomenon described as the emergence of resistant subpopulation cells within a single susceptible strain that can tolerate higher concentrations of fluconazole above the minimal inhibitory concentration (MIC) level.

Summary

We found lower FLC-MICs (0.12–64 mg/L) than LHF (8–128 mg/L). Highly heteroresistant adapted subpopulations (256 mg/L) was found in minority (9%) strains, but importantly, 33% showed low FLC-MIC (8 mg/L). We concluded for similar LHF in both species, but higher LHF in clinical strains in comparison to environmental ones. Our findings stressed that the LHF is not correlated to species and pretty is strain-dependent and alert about high heteroresistant subpopulations that hardly reverts to the original LHF even upon the removal of drug pressure.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (process number 2013/04567-5). We thank Dr. Marcio Rodrigues (Universidade Federal do Rio de Janeiro, Brazil) for kindly providing strain of C. neoformans H99. We thank Allan Antonio Kubo, Catia Regina Costa, Gisele Monteiro Santo Pedro, Gislene Palmeira Lucchi, Hélid Raquel Lautenschlaeger Rodrigues De Lucca, Olga Maria Diniz, and Sylvana Kwong Arregui Bay from Instituto Adolfo Lutz - Rio Claro, and Andrés Avelino Baez from Instituto Adolfo Lutz – São Paulo for excellent technical support.

Author information

Authors and Affiliations

  1. Graduate Program of the Disease Control Coordination, Secretary of Health, São Paulo, Brazil

    L. M. Feliciano

  2. Mycology Department, Instituto Adolfo Lutz, Rio Claro, São Paulo, Brazil

    S. D. P. Ramos, M. W. Szeszs, M. A. Martins, L. X. Bonfietti, R. A. Oliveira, D. C. S. Santos, L. H. Fadul, D. F. Silva & M. S. C. Melhem

  3. São Paulo University, São Paulo, Brazil

    C. R. Paula

  4. Oswaldo Cruz Foundation, Evandro Chagas Clinical Research Institute, Rio de Janeiro, Brazil

    L. Trilles

  5. Disciplina de Doenças Infecciosas Parasitárias, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil

    L. E. A. Silva, K. Ferreira-Paim, D. J. Mora, A. A. Andrade, P. R. Silva & M. L. Silva-Vergara

  6. São Paulo Federal University, São Paulo, Brazil

    T. N. Roberto

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  1. L. M. Feliciano
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  19. M. S. C. Melhem
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Corresponding author

Correspondence to M. S. C. Melhem.

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Feliciano, L.M., Ramos, S.D.P., Szeszs, M.W. et al. Heteroresistance to Fluconazol in Clinical and Environmental Brazilian Strains of Cryptococcus neoformans/C. gattii Species Complex. Curr Fungal Infect Rep 11, 190–196 (2017). https://doi.org/10.1007/s12281-017-0298-1

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