Chapter 34 : Antifungal Mechanisms of Action and Resistance

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The development of antifungal resistance is complex and relies on multiple host and microbial risk factors. In , specific resistance to triazole drugs results from selection pressure caused by drug exposure. The echinocandins are broadly active against a wide range of fungi without cross-resistance to existing antifungal agents and therefore are effective against azole-resistant yeasts and molds. Importantly, due to their critical effect on the cell wall, echinocandins are fungicidal with yeasts. Secondary or acquired resistance emerges in previously susceptible isolates during or after antifungal drug exposure. In , this kind of resistance is mainly associated with exposure to triazole drugs. The ultimate role of susceptibility testing is to detect potential clinically resistant isolates. For this purpose, two procedures have been extensively employed, and it has been demonstrated that they identify resistant samples and/or molds with high MICs of antifungal drugs. The characterization of phenotypic resistance in clinical isolates can help in evaluating their frequency and suggest possible therapeutic options. Detection of well-defined resistance mechanisms can serve as surrogate markers for phenotypic resistance. Epidemiological surveillance is necessary to detect trends in azole resistance and to anticipate resistance emergence against new antifungal drugs in clinical use.

Citation: Perlin D, Mellado E. 2009. Antifungal Mechanisms of Action and Resistance, p 457-466. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch34
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Figure 1.

Cyp51A-related resistance mechanisms to azoles. The antifungal drugs noted are as follows: ITC, itraconazole; VRC, voriconazole; PSC, posaconazole; RVC, ravuconazole. The “r” superscript connotes resistance.

Citation: Perlin D, Mellado E. 2009. Antifungal Mechanisms of Action and Resistance, p 457-466. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch34
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Table 1.

Principal antifungal drugs, modes of action, and specific targets

Citation: Perlin D, Mellado E. 2009. Antifungal Mechanisms of Action and Resistance, p 457-466. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch34

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