Combined action of micafungin, a new echinocandin, and human phagocytes for antifungal activity against Aspergillus fumigatus.
Micafungin, a new echinocandin, inhibits fungal cell wall beta-glucan synthesis. We postulated micafungin and host phagocytic cells could act together in damaging fungi. Using the metabolic XTT assay, micafungin alone (0.01 and 0.10 microg/ml) inhibited Aspergillus fumigatus germlings by 48% and 61%, respectively. Polymorphonuclear neutrophils (PMNs) inhibited germlings by 53%. Micafungin at 0.01 or 0.10 microg/ml and PMNs resulted in additive inhibition, 82% and 99%, respectively. Monocyte-derived macrophage (MDM) monolayers inhibited germling growth by 66%; micafungin (0.01 or 0.10 microg/ml) alone inhibited by 32% and 42%, respectively. MDMs and micafungin (0.01 or 0.10 microg/ml) caused an additive inhibition of growth, 85% and 95%, respectively. Hyphae were generated by incubation of conidia for 24 h with or without micafungin. PMNs alone, added to hyphae, inhibited growth by 19% in the subsequent 20 h. Hyphae generated in the presence of micafungin (0.10 microg/ml) and subsequently cultured with micafungin for 24 h inhibited growth by 64%. PMNs plus micafungin resulted in 82% inhibition. Monocytes alone inhibited hyphal growth by only 5%. Hyphae produced in the presence of micafungin (0.01 microg/ml) and incubated again with micafungin for 24 h inhibited growth by 47%; combination with monocytes resulted in 62% inhibition. These data indicate that micafungin inhibits growth of tissue forms of A. fumigatus, and phagocytes and micafungin together have an additive effect. These findings support the thesis that the greater efficacy of micafungin in vivo compared with in vitro could be due to combined effect of phagocytic cells and micafungin.
Choi
Jung-Hyun
JH
Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA.
Brummer
Elmer
E
Stevens
David A
DA
D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development*; D054714:Echinocandins; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests / Q000379:methods; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010586:Phagocytes / Q000276:immunology*; D013778:Tetrazolium Salts / Q000378:metabolism
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D000077551:Micafungin