Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus in vitro.
Statins (anticholesterol drugs) inhibit HMG-CoA reductase, which is a key rate-limiting enzyme in the synthesis of sterols in fungi. We therefore investigated the in vitro inhibitory activity of various statins against Aspergillus fumigatus alone and in combination with antifungal drugs. Fresh conidial suspensions from 10 clinical isolates of A. fumigatus were obtained. The MIC and minimum fungicidal concentration (MFC) were determined by the Clinical and Laboratory Standards Institute M-38A protocol and the fungicidal activity by time-kill study. Fluvastatin (FST) showed good activity (MIC, 2 mg/L; MFC, 4 mg/L) against A. fumigatus; other statins had no activity (MIC > or = 256 mg/L). FST enhanced the activity of caspofungin (CFG) against A. fumigatus; subinhibitory concentrations of FST in combination with CFG showed >99.9% killing of A. fumigatus conidia, whereas either drug alone showed poor activity at subinhibitory concentrations. FST potentiated the antifungal activity of CFG but displayed no specific interaction with voriconazole or amphotericin B.
Natesan
Suganthini Krishnan
SK
Department of Internal Medicine/Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48201, USA. skrishn@med.wayne.edu
Chandrasekar
Pranatharthi H
PH
Alangaden
George J
GJ
Manavathu
Elias K
EK
D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D000077336:Caspofungin; D015169:Colony Count, Microbial; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability
D000935:Antifungal Agents; D054714:Echinocandins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D055666:Lipopeptides; D000077340:Fluvastatin; D000077336:Caspofungin