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Diagn Microbiol Infect Dis. 2001 Feb;39(2):99-103.

The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus.

Author information

1
Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA. chiller@ieland.stanford.edu

Abstract

The collaboration between human effector cells and caspofungin (MK-0991), a 1,3-beta-D glucan synthase inhibitor, was studied for antifungal activity against Aspergillus fumigatus. Caspofungin was co-cultured for 24h with either human monocytes (Monos), monocyte-derived macrophages (MDM), or polymorphonuclear neutrophils (PMN) against germlings of A. fumigatus and antifungal activity assessed using the XTT metabolic assay. Caspofungin at 0.1 micorg/ml and 0.05 microg/ml or Monos alone against germlings caused significant inhibition. Microscopically this was correlated with less growth and stunted malformed hyphae. The addition of caspofungin at 0.1 microg/ml and 0.05 microg/ml to the monocyte cultures increased antifungal activity. The inhibition of the combination was significantly greater than drug alone (P <.01) and Monos alone (P <.01). MDM against Aspergillus germlings inhibited hyphal growth. The combination of caspofungin at 0.1 microg/ml and 0.05 microg/ml to the macrophage cultures increased antifungal activity. The growth inhibition by the combination was significantly greater than drug alone (P <.01) and MDM alone (P <.01). There was no significant interference with or enhancement of PMNs and caspofungin. These data support the activity of caspofungin against A. fumigatus in vitro, and indicates a cooperative activity with human effector cells. This suggests caspofungin in vivo would have increased efficacy as it combines with host defenses against A. fumigatus.

PMID:
11248522
DOI:
10.1016/s0732-8893(00)00236-4
[Indexed for MEDLINE]

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