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(New) Methods for Detection of Aspergillus fumigatus Resistance in Clinical Samples
Jeffrey D Jenks1, Birgit Spiess2, Dieter Buchheidt2
1Department of Medicine, University of California San Diego, San Diego, CA 92103, USA.
Purpose Of Review:
The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of Aspergillus fumigatus with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to Aspergillus.
Recent Findings:
New molecular-based approaches for detecting triazole resistance to Aspergillus, real-time polymerase chain reaction (PCR) to detect mutations to the Cyp51A protein, have been developed which are able to detect most triazole-resistant A. fumigatus strains in patients with invasive aspergillosis.
Summary:
Over the last few years, a number of non-culture-based methods for molecular detection of Aspergillus triazole resistance have been developed that may overcome some of the limitations of culture. These molecular methods are therefore of high epidemiological and clinical relevance, mainly in immunocompromised patients with hematological malignancies, where culture has particularly limited sensitivity. These assays are now able to detect most triazole-resistant Aspergillus fumigatus strains. Given that resistance rates vary, clinical utility for these assays still depends on regional resistance patterns.
Insights
New molecular methods can now detect triazole resistance in Aspergillus fumigatus, addressing limitations of traditional culture methods. These advancements are crucial for managing invasive aspergillosis, especially in immunocompromised patients.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Diagnostics
Background:
- Invasive aspergillosis incidence is rising, with increasing resistance of Aspergillus fumigatus to key triazole antifungals like voriconazole and isavuconazole.
- Current culture-based methods for detecting triazole resistance are the gold standard but are slow and lack sensitivity.
- There is a critical need for improved diagnostic methods to identify triazole resistance in Aspergillus.
Purpose of the Study:
- To review and update on non-culture-based methods for detecting triazole resistance patterns in Aspergillus species.
- To highlight the clinical and epidemiological relevance of novel diagnostic approaches.
Main Methods:
- Development of molecular-based approaches, specifically real-time polymerase chain reaction (PCR).
- Detection of mutations in the Cyp51A gene, a key indicator of triazole resistance.
- Evaluation of these methods for identifying triazole-resistant Aspergillus fumigatus strains.
Main Results:
- New real-time PCR assays can effectively detect mutations conferring triazole resistance in Aspergillus fumigatus.
- These molecular methods demonstrate high sensitivity in identifying resistant strains in patients with invasive aspergillosis.
- The assays can detect most common triazole-resistant Aspergillus fumigatus strains.
Conclusions:
- Non-culture-based molecular methods offer a promising alternative to traditional culture techniques for Aspergillus triazole resistance detection.
- These methods are particularly valuable in immunocompromised patients, such as those with hematological malignancies, where culture sensitivity is limited.
- The clinical utility of these assays is influenced by regional variations in resistance rates.
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