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Azole-Resistant Aspergillosis: Epidemiology, Molecular Mechanisms, and Treatment
Anuradha Chowdhary1, Cheshta Sharma1, Jacques F Meis2,3
1Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, India.
Abstract:
Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis. Lately, increased azole resistance in A. fumigatus has become a significant challenge in effective management of aspergillosis. Earlier studies have brought to light the contribution of non-cyp51 mutations along with alterations in cyp51A gene resulting in azole-resistant phenotypes of A. fumigatus. This review highlights the magnitude of azole-resistant aspergillosis and resistance mechanisms implicated in the development of azole-resistant A. fumigatus and address the therapeutic options available.
Insights
Azole resistance in Aspergillus fumigatus is a growing challenge for treating fungal infections. This review examines resistance mechanisms and therapeutic options for azole-resistant aspergillosis.
Area of Science:
- Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Aspergillus fumigatus and Aspergillus flavus are key pathogens causing pulmonary and other syndromes.
- Invasive, chronic, and allergic manifestations of Aspergillus infections are clinically significant.
- Triazoles are primary treatments, but rising azole resistance complicates management.
Purpose of the Study:
- To review the prevalence and mechanisms of azole resistance in Aspergillus species.
- To discuss the clinical impact of azole-resistant aspergillosis.
- To explore current and potential therapeutic strategies.
Main Methods:
- Literature review of studies on azole resistance in Aspergillus.
- Analysis of genetic mutations (e.g., in cyp51A) contributing to resistance.
- Synthesis of information on clinical manifestations and treatment outcomes.
Main Results:
- Increased azole resistance, particularly in A. fumigatus, poses a significant clinical threat.
- Resistance mechanisms involve both cyp51A alterations and other genetic mutations.
- Effective management is challenged by limited therapeutic options.
Conclusions:
- Azole resistance in Aspergillus is a critical issue requiring urgent attention.
- Understanding resistance mechanisms is key to developing new treatment strategies.
- Further research into novel antifungals and combination therapies is essential.
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