Killing rates exerted by caspofungin in 50% serum and its correlation with in vivo efficacy in a neutropenic murine model against Candida krusei and Candida inconspicua

Renátó Kovács, R. Gesztelyi, Réka Berényi, Marianna Domán, G. Kardos, B. Juhász, László Majoros

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Abstract

Killing rates (K) of 1-32 μg 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 μg ml-1 in RPMI-1640 and 2 μg ml-1 in serum) and three Candida inconspicua clinical isolates (MIC ranges 0.06-0.12 μg ml-1 in RPMI-1640 and 0.25-0.5 \μg ml-1 in serum), against C. krusei ATCC 6258 and against one C. krusei isolate that was resistant to echinocandins (MIC 8 μg ml-1 in RPMI-1640 and 32 μg 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) μg ml-1 caspofungin for C. krusei and C. inconspicua clinical isolates, respectively. In 50% serum, mean Kvalue ranges at 1-32 and 4-32 μg 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-1 significantly decreased the fungal tissue burden of C. inconspicua in the kidneys (P-1 caspofungin were effective (P-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 μg 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.

Original languageEnglish
Pages (from-to)186-194
Number of pages9
JournalJournal of Medical Microbiology
Volume63
Issue numberPART 2
DOIs
Publication statusPublished - Feb 2014

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  • Microbiology

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Killing rates exerted by caspofungin in 50% serum and its correlation with in vivo efficacy in a neutropenic murine model against Candida krusei and Candida inconspicua. / Kovács, Renátó; Gesztelyi, R.; Berényi, Réka; Domán, Marianna; Kardos, G.; Juhász, B.; Majoros, László.

In: Journal of Medical Microbiology, Vol. 63, No. PART 2, 02.2014, p. 186-194.

Research output: Contribution to journalArticle

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abstract = "Killing rates (K) of 1-32 μg 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 μg ml-1 in RPMI-1640 and 2 μg ml-1 in serum) and three Candida inconspicua clinical isolates (MIC ranges 0.06-0.12 μg ml-1 in RPMI-1640 and 0.25-0.5 \μg ml-1 in serum), against C. krusei ATCC 6258 and against one C. krusei isolate that was resistant to echinocandins (MIC 8 μg ml-1 in RPMI-1640 and 32 μg 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) μg ml-1 caspofungin for C. krusei and C. inconspicua clinical isolates, respectively. In 50{\%} serum, mean Kvalue ranges at 1-32 and 4-32 μg 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-1 significantly decreased the fungal tissue burden of C. inconspicua in the kidneys (P-1 caspofungin were effective (P-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 μg 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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