Current and emerging azole antifungal agents
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Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.
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Azoles deplete the Candida cell membrane of ergosterol and cause accumulation of toxic 14α-methylated sterols, decreasing membrane fluidity and in most cases inhibiting cell growth.
“As a result of the action of azoles, the Candida cell membrane is depleted of ergosterol and accumulates other toxic 14α-methylated sterols. Subsequently, this causes the decrease in membrane fluidity and, in most of the cases, inhibits cell growth [20].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [20]
The in vitro anti-Candida activity of posaconazole and ravuconazole appears to be good.
“The in vitro anti-Candida activity of the other azoles under active development (posaconazole and ravuconazole) also appears to be good [50].”
From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [50]
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- Authors
- Sheehan, D. J., Hitchcock, C. A., & Sibley, C. M.
- Affiliations
- Pfizer (United States) (US)
- Pfizer (United Kingdom) (GB)
- <!--label omitted: 3-->Medical/Scientific Communications, Inc., Bloomfield, New Jersey3
- Venue
- Clinical Microbiology Reviews
- Publisher
- American Society for Microbiology
- Published
- 1999-01
- Volume
- 12
- Issue
- 1
- Pages
- 40-79
- ISSN
- 0893-8512 (ISSN-L)
- 1098-6618
- PMC
- PMC88906
- OpenAlex
- W2157428610
- Cited by
- 1,137
- References
- 227
- Citations by year
- 2026: 30 · 2025: 40 · 2024: 42 · 2023: 42 · 2022: 37 · 2021: 34 · 2020: 49 · 2019: 35 · 2018: 51 · 2017: 39 · 2016: 55 · 2015: 53 · 2014: 47 · 2013: 40 · 2012: 53
- FWCI
- 24.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Microbiology Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- azole antifungals, triazoles, fluconazole, itraconazole, amphotericin B, ketoconazole, antifungal resistance, in vitro susceptibility testing, systemic fungal infection, superficial fungal infections, opportunistic fungal infection, endemic fungal infection, combination antifungal therapy, emerging fungal pathogens
- MeSH terms
- Animals, Antifungal Agents, Azoles, Humans, Microbial Sensitivity Tests, Mycoses, Drug Design
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