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Comparison of In Vitro and Vivo Efficacy of Caspofungin Against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans

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Abstract

Caspofungin activity was determined in vitro and in vivo against three Candida orthopsilosis, three C. metapsilosis, two C. parapsilosis sensu stricto and two C. albicans isolates. MIC values and killing activity were determined in RPMI-1640 plus 50 % human serum. Neutropenic (cyclophosphamide-treated) mice were infected intravenously. Five-day intraperitoneal treatment with caspofungin was started after 24 h postinfection. Kidney burden was analyzed using the Kruskal–Wallis test with Dunn’s post-test. In killing studies, caspofungin was fungistatic and fungicidal against C. albicans at ≥0.25 and ≥2 μg/ml concentrations, respectively. Caspofungin was fungistatic at ≥8–16, ≥2–8 and at ≥2–8 μg/ml against C. parapsilosis, C. orthopsilosis and C. metapsilosis, respectively. In the murine model, C. albicans was inhibited by 1, 2 and 5 mg/kg of caspofungin (P < 0.001 compared to the controls). Against C. parapsilosis, only 5 mg/kg caspofungin was effective against both isolates (P < 0.05). Two and five mg/kg of caspofungin was effective against all C. orthopsilosis and C. metapsilosis isolates (P < 0.05 to <0.001). Serum-based killing tests proved to be useful in predicting in vivo efficacy of caspofungin against four Candida species. Caspofungin at clinically attainable concentrations proved to be effective against all four species.

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Acknowledgments

Caspofungin pure powder was kindly provided by Merck Research Laboratories, Rahway, NJ., USA. R. Földi was supported by a Richter Gedeon Pharma PhD scholarship, L. Majoros was supported by a Bolyai Research Scholarship of the Hungarian Academy of Sciences. The work of R. Földi and L. Majoros was supported by the TÁMOP 4.2.1./B-09/1/KONV-2010-0007 project (New Hungary Development Plan, co-financed by the European Social Fund and the European Regional Development Fund). L. Majoros received conference travel grants from MSD and Pfizer.

Conflict of interest

R. Földi was supported by a Richter Gedeon Pharma PhD scholarship, L. Majoros was supported by a Bolyai Research Scholarship of the Hungarian Academy of Sciences. The work of R. Földi and L. Majoros was supported by the TÁMOP 4.2.1./B-09/1/KONV-2010-0007 project (New Hungary Development Plan, co-financed by the European Social Fund and the European Regional Development Fund).

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Authors and Affiliations

  1. Department of Medical Microbiology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98., 4032, Debrecen, Hungary

    Richárd Földi, Renátó Kovács, Gábor Kardos, Réka Berényi, Judit Szilágyi, Julianna Mózes & László Majoros

  2. Department of Pharmacology and Pharmacodynamics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Rudolf Gesztelyi & Béla Juhász

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  1. Richárd Földi
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  2. Renátó Kovács
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  7. Judit Szilágyi
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  9. László Majoros
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Correspondence to László Majoros.

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Földi, R., Kovács, R., Gesztelyi, R. et al. Comparison of In Vitro and Vivo Efficacy of Caspofungin Against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans . Mycopathologia 174, 311–318 (2012). https://doi.org/10.1007/s11046-012-9554-7

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