Triazole resistance in Aspergillus fumigatus: recent insights and challenges for patient management
P P A Lestrade1, J F Meis2, W J G Melchers3
1Department of Medical Microbiology, VieCuri Medical Centre, Venlo, the Netherlands.
Background:
Triazole resistance in Aspergillus fumigatus is widespread and threatens first-line triazole therapy in patients with Aspergillus diseases.
Objectives:
To give an overview of the microbiology, epidemiology and clinical significance of triazole resistance in aspergillosis.
Sources:
PubMed search for articles on resistance in Aspergillus species.
Content:
Triazoles are not mutagenic but select resistance when spontaneous mutations occur that are better able to proliferate in the triazole-containing environment. The major target for resistance mutations involves the Cyp51A gene, encoding an enzyme involved in cell wall synthesis. Triazole-resistance selection environments include patient treatment and organic matter containing triazole fungicide residues. Reported resistance frequencies vary widely between countries and hospitals, and resistance significantly complicates the diagnosis and treatment of Aspergillus diseases. Cultures may harbour various resistance phenotypes and multiple colonies must be analysed to detect resistance. PCR tests have become available for resistance detection in culture-negative patients, but show limited sensitivity. Individuals with triazole-resistant invasive aspergillosis have a 21% higher day-42 mortality compared with triazole-susceptible infection, and to prevent excess mortality resistant cases require first-line therapy that covers resistance. The recent ESCMID-ECMM-ERS Aspergillus guideline recommends resistance testing in A. fumigatus and local resistance surveillance. If resistance rates exceed 10% liposomal amphotericin B or triazole and echinocandin first-line therapy should be considered.
Implications:
Triazole resistance significantly complicates the management of aspergillosis and multidisciplinary research from a 'One-health' perspective is required to retain the triazole class for medical use.
Insights
Triazole resistance in Aspergillus fumigatus is a growing threat to antifungal therapy. Early detection and multidisciplinary research are crucial to preserve triazole effectiveness for treating aspergillosis.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Widespread triazole resistance in Aspergillus fumigatus compromises standard antifungal treatments for aspergillosis.
- Resistance arises from spontaneous mutations, often in the Cyp51A gene, enabling fungal proliferation in triazole-exposed environments.
- Selection pressures include patient treatment and agricultural fungicide residues.
Purpose of the Study:
- To provide a comprehensive overview of the microbiology, epidemiology, and clinical impact of triazole resistance in aspergillosis.
- To highlight the challenges in diagnosing and treating resistant Aspergillus infections.
- To inform clinical guidelines and future research directions.
Main Methods:
- Literature review using PubMed database.
- Focused search on articles concerning resistance mechanisms and clinical significance in Aspergillus species.
- Analysis of reported resistance frequencies and mortality data.
Main Results:
- Triazole resistance significantly increases mortality in invasive aspergillosis (21% higher day-42 mortality).
- Detection of resistance requires careful culture analysis; PCR tests have limitations.
- Resistance frequencies vary globally, necessitating local surveillance and guideline adherence.
Conclusions:
- Triazole resistance poses a significant challenge to aspergillosis management.
- Multidisciplinary, 'One Health' approaches are essential to maintain the utility of triazoles in medicine.
- Implementing resistance testing and considering alternative therapies are critical for patient outcomes.
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