The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus.
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.
Chiller
T
T
Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA. chiller@ieland.stanford.edu
Farrokhshad
K
K
Brummer
E
E
Stevens
D A
DA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010455:Peptides
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010455:Peptides