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Present Situation and Perspectives of Antimycotics with Systemic Effect


Authors: J. Haber
Authors‘ workplace: I. interní klinika 1. LF UK a VFN, Praha
Published in: Čas. Lék. čes. 2001; : 596-604
Category:

Overview

Spectrum of antimycotics used in treatment of systemic mycoses is comparatively poor. The oldest and till presentreceived „golden standard“ is polyen amphotericin B (AmB). It has the widest spectrum of effects and has the lowestincidence of resistances. However, the therapy can be accompanied by manifestations of toxicity, namely that ofnephrotoxicity. „Lipoid“ form of AmB (Abelcet, Amphocil, AmBisome) with only 20% risk of nephrotoxicity partlysolved the problem. Wider use of these drugs is hindered by their high price. The azoles group (ketoconazole,fluconazole, itraconazole) today represents the most frequently used group of antimycotics; triazols of the 3rdgeneration (variconazole, posaconazole, ravuconazole) broaden the spectrum of effects namely to aspergil infections.In the future substances with a different target structure will be used. According the mechanism of effect they canbe classified as echinocandins (inhibition of b-glucane synthesis), echinocandins (inhibition of chitin synthesis),sordarines (selective inhibitors of proteosynthesis), pradimicines (cell lysis by binding on manoproteins). The risingoccurrence of resistance should be coped with inhibitors of the efflux pump (milbemycine). Clinical testing of allthese substances is already in progress, in some of them already in phase III.

Key words:
amphotericin B, nystatine, azoles, fluconazole, ketoconazole, itraconazole, variconazole, ravucona -zole, posaconazole, echinocandins, sordarines, pradimicines, efflux pump inhibitors.

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