期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 61, 期 5, 页码 1140-1144出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkn069
关键词
Aspergillus; echinocandins; pharmacodynamics
Objectives: The safety and concentration-dependent pharmacodynamic characteristics of the echinocandins make them ideal candidates for dosage escalation in the treatment of aspergillosis. However, paradoxical attenuation of antifungal activity with increasing doses has been reported for some echinocandins in experimental models of invasive pulmonary aspergillosis (IPA). Methods: We compared the activity of micafungin and caspofungin administered over a wide dosing range that encompasses clinical exposures (0.25-10 mg/kg) in a neutropenic murine model of IPA. Results: Both echinocandins exhibited dose-dependent reductions in fungal burden; however, caspofungin displayed a relatively steeper dose-response curve with a modest paradoxical increase in fungal burden that was not seen in micafungin-treated animals. Equivalent activity was observed with both echinocandins at daily doses ranging from 4 to 10 mg/kg. Conclusions: Both micafungin and caspofungin exhibit dose-dependent pharmacodynamic activity in vivo in the treatment of neutropenic IPA. Both echinocandins were equivalent at dosages >= 4 mg/kg day.
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