Antilipid Therapy of Fungi
Source: Chin N-X, et al. Antimicrobial Agents Chemother 1997; 41:850-852.
Fluvastatin (lescol, sandoz pharmaceuticals) is the first wholly synthetic coenzyme A reductase inhibitor used for lowering cholesterol and is structurally distinct from the other cholesterol-lowering agents, pravastatin, lovastatin, and simvastatin (all of which are derived from a fermentation product of Aspergillus terreus). Chin et al demonstrated that, unlike the other three agents, fluvastatin has potent in vitro anti-fungal activity against various Candida species and filamentous fungi, including fluconazole-resistant C. albicans and C. tropicalis (at MICs above its usual concentration in plasma).
At concentrations of 16 to greater than 128 mcg/mL, fluvastatin inhibited 80% of the growth of C. albicans, C. tropicalis, and C. parapsilosis, and at 64-128 mcg/mL prevented any visible growth of several Candida strains, but it was less effective against C. glabrata and Cryptococcus neoformans. Fluvastatin (< 8 mcg/mL), in combination with either fluconazole or itraconazole, was four- to eight-fold more active than either azole alone; both azoles became fungicidal in the presence of fluvastatin against not only sensitive Candida strains, but resistant strains of C. albicans and C. tropicalis, as well as strains of C. neoformans. Synergy studies with amphotericin B demonstrated an additive effect. Further investigation in animal studies is being done, but fluvastatin may prove useful as a topical agent in the treatment of mucocutaneous or esophageal disease caused by certain Candida species.
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