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JAC Advance Access originally published online on April 4, 2008
Journal of Antimicrobial Chemotherapy 2008 62(1):149-152; doi:10.1093/jac/dkn144
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Time–kill studies investigating the killing activity of caspofungin against Candida dubliniensis: comparing RPMI-1640 and antibiotic medium 3

I. Varga1, G. Sóczó2, G. Kardos2 and L. Majoros2,*

1 Faculty of Dentistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary 2 Department of Medical Microbiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

Received 19 December 2007; returned 29 January 2008; revised 6 March 2008; accepted 10 March 2008

* Corresponding author. Tel: +36-52-411-717/54501; Fax: +36-52-414-948; E-mail: major{at}med.unideb.hu

Objectives: We evaluated the in vitro activity of caspofungin against Candida dubliniensis strains using MIC and minimum fungicidal concentration (MFC) measurements and time–kill methodology.

Methods: We used six C. dubliniensis clinical isolates and the CD 36 type strain. MICs and MFCs of caspofungin were determined using the standard broth microdilution method with normal (103 cells/mL) and elevated (105 cells/mL) starting inocula in RPMI-1640 and antibiotic medium 3 (AM3). MIC was determined after 24 h, and plating for MFC determination was performed after 48 h. In time–kill tests, all strains were tested at 0.06–16 mg/L caspofungin concentrations in RPMI-1640 and AM3.

Results: In RPMI-1640, the MIC range was 0.06–8 mg/L. Trailing growth was observed regardless of the starting inoculum after 48 h, but not after 24 h. In AM3 regardless of starting inoculum, MICs were 0.03 mg/L. After 48 h, trailing was not detected; two isolates grew at a concentration of 8 mg/L using 105 cells/mL as the starting inoculum [paradoxical growth (PG)]. All MFCs in RPMI-1640 and AM3 were >8 and ≤0.12 mg/L, respectively. In AM3, all but a single isolate showed PG in the MFC tests. Time–kill tests confirmed the results obtained by MFC tests both in RPMI-1640 and AM3.

Conclusions: In vitro activity of caspofungin against C. dubliniensis depended on the starting inoculum and medium used. Using AM3 eliminated trailing from MIC determinations but not PG in MIC, MFC and time–kill tests.

Keywords: paradoxical growth , Eagle effect , fungicidal


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