Journal
JOURNAL OF MEDICAL MICROBIOLOGY
Volume 63, Issue -, Pages 186-194Publisher
SOC GENERAL MICROBIOLOGY
DOI: 10.1099/jmm.0.066381-0
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Funding
- New Hungary Development Plan - European Social Fund [TAMOP 4.2.2./B-10/1/-2010-0024]
- European Regional Development Fund [TAMOP 4.2.2./B-10/1/-2010-0024]
- 'National Excellence Program - Elaborating and Operating an Inland Student and Researcher Personal Support System' [TAMOP 4.2.4. A/2-11-1-2012-0001]
- European Union
- European Social Fund
- MSD
- Astellas
- Pfizer
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Killing rates (K) of 1-32 mu g ml(-1) caspofungin were determined in RPMI-1640 and in 50% serum using time-kill methodology against three Candida krusei (MICs of all three isolates 0.25 mu g ml(-1) in RPMI-1640 and 2 mu g ml(-1) in serum) and three Candida inconspicua clinical isolates (MIC ranges 0.06-0.12 mu g ml(-1) in RPMI-1640 and 0.25-0.5 fig ml(-1) in serum), against C. krusei ATCC 6258 and against one C. krusei isolate that was resistant to echinocandins (MIC 8 mu g ml(-1) in RPMI-1640 and 32 mu g ml(-1) in serum). In RPMI-1640, the highest mean K values were observed at 4 (-1.05 h(-1)) and 16 (-0.27 h(-1)) mu g ml(-1) caspofungin for C. krusei and C. inconspicua clinical isolates, respectively. In 500/o serum, mean K value ranges at 1-32 and 4-32 mu g ml(-1) concentrations for C. inconspicua and C. krusei were -1.12 to -1.44 and -0.42 to -0.57 h(-1), respectively. While K values against C. krusei in RPMI-1640 and 50% serum were comparable, serum significantly increased the killing rate against C. inconspicua (P<0.0003 for all tested concentrations). In a neutropenic murine model, daily caspofungin at 1, 2, 3, 5 and 15 mg kg(-1) significantly decreased the fungal tissue burden of C. inconspicua in the kidneys (P<0.05-0.001). Against C. krusei, doses of 3, 5 and 15 mg kg(-1) caspofungin were effective (P<0.05-0.01). All effective doses were comparably efficacious for both species. Only the highest 15 mg kg(-1) caspofungin dose was effective even against the echinocandin-resistant C. krusei isolate. In 50% serum, killing was concentration independent at effective concentrations (>= 4 and >= 1 mu g ml(-1) for C. krusei and C. inconspicua, respectively), suggesting that the efficacy of dose escalation is questionable. These in vitro results were also supported by the murine model.
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