Poor in vivo efficacy of caspofungin, micafungin and amphotericin B against wild-type Candida krusei clinical isolates does not correlate with in vitro susceptibility results

Abstract

We determined micafungin, caspofungin and amphotericin B (AMB) minimum inhibitory concentration (MICs) and killing rates in RPMI-1640 and in RPMI-1640 with 50% serum against three Candida krusei bloodstream isolates. MIC ranges in RPMI-1640 were 0.125–0.25, 0.25 and 0.125–0.5 mg/L, in RPMI-1640 with 50% serum, MICs were 64–128-, 8- and 4–16-fold higher, respectively. In RPMI-1640 micafungin and caspofungin at 1, 4, 16 and 32 mg/L as well as AMB at 2 mg/L were fungicidal against all isolates in ≤3.96, ≤4.42 and 14.96 h, respectively. In RPMI-1640 with 50% serum, caspofungin was fungicidal for all isolates only at 32 mg/L, micafungin and AMB were fungistatic. In neutropenic mice, 5 mg/kg caspofungin and 1 mg/kg AMB were ineffective against two of the three isolates. Thus, in vivo efficacy of echinocandins and AMB is weak or absent against C. krusei. Prescribers treating C. krusei infections with echinocandins should watch out for clinical resistance and therapeutic failure.

Keywords:

• Echinocandin susceptibility
• 50% serum
• killing rate
• neutropenic murine model

Acknowledgment

The authors thank Katalin Orosz-Tóth for the expert technical assistance.

Disclosure statement

No potential conflict of interests was reported by the author(s).

Additional information

Funding

L. Majoros received conference travel grants from MSD, Astellas and Pfizer. R. Kovács was supported by the TÁMOP 4.2.4. A/2-11-1-2012-0001 “National excellence Program-Elaborating and operating an inland student and researcher personal support system.” The project was subsidized by European Union and co-financed by the European Social Fund.

Notes on contributors

Tamás Kardos

Tamas Kardos, Renato Kovacs, István Varga and Laszlo Majoros participated in concept and design of the study. Acquisition of data was done by Tamas Kardos, Aliz Bozó, Zoltán Tóth, Fruzsina Nagy. Analysis of data was also done by Renato Kovacs, Gabor Kardos and Laszlo Majoros. Tamas Kardos, Laszlo Majoros and Gabor Kardos contributed to article drafting. All of the authors approved the manuscript.

Istvan Varga

Tamas Kardos, Renato Kovacs, István Varga and Laszlo Majoros participated in concept and design of the study. Acquisition of data was done by Tamas Kardos, Aliz Bozó, Zoltán Tóth, Fruzsina Nagy. Analysis of data was also done by Renato Kovacs, Gabor Kardos and Laszlo Majoros. Tamas Kardos, Laszlo Majoros and Gabor Kardos contributed to article drafting. All of the authors approved the manuscript.

László Majoros

Tamas Kardos, Renato Kovacs, István Varga and Laszlo Majoros participated in concept and design of the study. Acquisition of data was done by Tamas Kardos, Aliz Bozó, Zoltán Tóth, Fruzsina Nagy. Analysis of data was also done by Renato Kovacs, Gabor Kardos and Laszlo Majoros. Tamas Kardos, Laszlo Majoros and Gabor Kardos contributed to article drafting. All of the authors approved the manuscript.