Activity of cilofungin against Coccidioides immitis: differential in vitro effects on mycelia and spherules correlated with in vivo studies.
Cilofungin, a new antifungal drug, was found to inhibit mycelial growth of Coccidioides immitis. Light and electron microscopic observations indicated delay in development of the outer hyphal wall. Cilofungin also blocked incorporation of the chitin substrate, N-acetylglucosamine, into mycelia. However, when C. immitis was grown under conditions that induced spherule development, drug effects were dramatically decreased. Furthermore, efficacy of cilofungin in treatment of murine coccidioidomycosis could not be demonstrated. These studies indicate that glucan-synthase inhibitors have activity against C. immitis, and other compounds with different pharmacologic properties or in combination with other antifungal drugs may exploit this biologic effect.
Galgiani
J N
JN
Medical Service, Veterans Administration Medical Center, Tucson, AZ 85723.
Sun
S H
SH
Clemons
K V
KV
Stevens
D A
DA
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003045:Coccidioides / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D003047:Coccidioidomycosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D054714:Echinocandins; D005260:Female; D006801:Humans; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009504:Neutrophils / Q000382:microbiology; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology
D000935:Antifungal Agents; D054714:Echinocandins; D010455:Peptides; D010456:Peptides, Cyclic; C042101:cilofungin