Journal
JOURNAL OF FUNGI
Volume 6, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/jof6020067
Keywords
Azole resistance; Aspergillus fumigatus; AsperGenius (R) multiplex real-time PCR assay; G54; M220; TR46/Y121F/T289A; TR34/L98H; chronic pulmonary aspergillosis; allergic bronchopulmonary aspergillosis
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Funding
- Indian Council of Medical Research
- Government of India, New Delhi, India
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Aspergillosis due to azole-resistantAspergillus fumigatusis a worldwide problem with major therapeutic implications. In patients with invasive aspergillosis, a low yield of fungal cultures results in underestimation of azole resistance. To detect azole resistance inA. fumigatus, we applied the AsperGenius (R) Resistance multiplex real-time polymerase chain reaction (PCR) assay to detect TR34/L98H, and TR46/T289A/Y121F mutations and the AsperGenius (R) G54/M220 RUO PCR assay to detect G54/M220 mutations directly in bronchoalveolar lavage (BAL) samples of 160 patients with chronic respiratory diseases in Delhi, India. Only 23% of samples were culture-positive compared to 83% positivity byA. fumigatusspecies PCR highlighting concerns about the low yield of cultures. Notably, 25% of BAL samples (33/160 patients) had azole resistance-associated mutation by direct detection using PCR assay. Detection of resistance-associated mutations was found mainly in 59% and 43% patients with chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA), respectively. Overall, a G54 mutation, conferring itraconazole resistance, was the predominant finding in 87.5% and 67% of patients with CPA and ABPA, respectively. In culture-negative, PCR-positive samples, we detected azole-resistant mutations in 34% of BAL samples. Azole resistance in chronicAspergillusdiseases remains undiagnosed, warranting standardization of respiratory culture and inclusion of rapid techniques to detect resistance markers directly in respiratory samples.
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