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Killing Activity of Micafungin Against Candida albicans, C. dubliniensis and Candida africana in the Presence of Human Serum

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Abstract

We compared killing activity of micafungin in time-kill experiments in RPMI-1640 with and without 50% serum against Candida albicans, Candida dubliniensis and Candida africana reference strains and clinical isolates. Killing rates (k values) were determined for each strain and concentration. In RPMI-1640 MIC ranges were 0.015–0.03, 0.015–0.03 and 0.015 mg/L against C. albicans, C. dubliniensis and C. africana, respectively. In 50% serum MIC values for the three species increased 16- to 64-fold. In RPMI-1640 micafungin was fungicidal against two of three C. albicans isolates at 16 and 32 mg/L within 14.54 h and fungistatic against all C. africana and C. dubliniensis. Fifty per cent serum significantly decreased the growth rate of C. africana, but not of the other two species; weak in vivo replication ability of C. africana was confirmed in murine model. In 50% serum micafungin at 0.25 and 1 mg/L did not inhibit any of the three species (k values were always negative). Micafungin killing rate in 50% serum at 4, 16 and 32 mg/L was significantly decreased for C. albicans, but increased for C. dubliniensis compared to RPMI-1640. Killing activity of micafungin against C. africana was comparable or higher in 50% serum than in RPMI-1640. Although micafungin is a highly protein-bound drug, it was equally effective against the species of the C. albicans complex in 50% serum at therapeutic trough concentration (4 mg/L). Both in vitro and in vivo data confirmed the low virulence of C. africana compared to the two sibling species.

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Acknowledgements

The authors thank Guillermo Quindós for the C. africana clinical isolate. Micafungin pure powder was kindly provided by Astellas. R. Kovács was supported by the TÁMOP 4.2.4. A/2-11-1-2012-0001.

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Authors and Affiliations

  1. Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Nagyerdei krt. 98., 4032, Hungary

    Renátó Kovács, Qasem Saleh, Aliz Bozó, Zoltán Tóth, Gábor Kardos & László Majoros

  2. Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary

    Renátó Kovács

  3. Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Rudolf Gesztelyi

  4. Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Tamás Kardos

  5. Faculty of Health, University of Miskolc, Miskolc, Hungary

    István Takacs

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  1. Renátó Kovács
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Kovács, R., Saleh, Q., Bozó, A. et al. Killing Activity of Micafungin Against Candida albicans, C. dubliniensis and Candida africana in the Presence of Human Serum. Mycopathologia 182, 979–987 (2017). https://doi.org/10.1007/s11046-017-0178-9

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