Triazole resistance in Aspergillus fumigatus: recent insights and challenges for patient management.

ABSTRACT

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.