Current and emerging azole antifungal agents

D J Sheehan1, C A Hitchcock, C M Sibley

  • 1Pfizer Pharmaceuticals Group, Pfizer Inc., New York, New York 10017-5755, USA. sheehd@pfizer.com

Insights

Newer azole antifungals offer safer treatment options for fungal infections. However, emerging resistance necessitates exploring combination therapies and next-generation azoles for improved efficacy against challenging pathogens.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Azole antifungals have advanced treatment for opportunistic and endemic fungal infections since the 1990s.
  • Fluconazole and itraconazole demonstrate improved safety profiles compared to older agents like amphotericin B and ketoconazole.
  • Despite progress, serious fungal infections persist as a therapeutic challenge, compounded by the emergence of drug resistance.

Purpose of the Study:

  • To review the current and future applications of available azole antifungal agents.
  • To provide an overview of in vitro susceptibility testing and clinical resistance trends.
  • To discuss the development of second-generation triazoles for broader pathogen coverage and resistant strains.

Main Methods:

  • Literature review of azole antifungal research and clinical applications.
  • Analysis of in vitro susceptibility data and emerging resistance patterns.
  • Evaluation of second-generation triazoles in development.

Main Results:

  • Azoles like fluconazole and itraconazole are safer and effective for various fungal infections.
  • Clinical resistance to existing azoles is a growing concern, impacting treatment efficacy.
  • Combination therapy with azoles and agents of different mechanisms shows promise for enhanced outcomes.

Conclusions:

  • Current azoles provide valuable treatment options, but resistance necessitates ongoing research.
  • Combination therapies and novel second-generation triazoles are crucial for managing difficult-to-treat and resistant fungal infections.
  • Continued development of azole antifungals is vital to combat evolving fungal pathogens.

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