1887

Abstract

Killing rates () of 1–32 µg ml caspofungin were determined in RPMI-1640 and in 50 % serum using time–kill methodology against three (MICs of all three isolates 0.25 µg ml in RPMI-1640 and 2 µg ml in serum) and three clinical isolates (MIC ranges 0.06–0.12 µg ml in RPMI-1640 and 0.25–0.5 µg ml in serum), against ATCC 6258 and against one isolate that was resistant to echinocandins (MIC 8 µg ml in RPMI-1640 and 32 µg ml in serum). In RPMI-1640, the highest mean values were observed at 4 (−1.05 h) and 16 (−0.27 h) μg ml caspofungin for and clinical isolates, respectively. In 50 % serum, mean value ranges at 1–32 and 4–32 µg ml concentrations for and were −1.12 to −1.44 and −0.42 to −0.57 h, respectively. While values against in RPMI-1640 and 50 % serum were comparable, serum significantly increased the killing rate against (<0.0003 for all tested concentrations). In a neutropenic murine model, daily caspofungin at 1, 2, 3, 5 and 15 mg kg significantly decreased the fungal tissue burden of in the kidneys (<0.05–0.001). Against , doses of 3, 5 and 15 mg kg caspofungin were effective (<0.05–0.01). All effective doses were comparably efficacious for both species. Only the highest 15 mg kg caspofungin dose was effective even against the echinocandin-resistant isolate. In 50 % serum, killing was concentration independent at effective concentrations (≥4 and ≥1 µg ml for and , respectively), suggesting that the efficacy of dose escalation is questionable. These results were also supported by the murine model.

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2014-02-01
2020-12-02
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