Azole Resistance in Aspergillus fumigatus from Respiratory Samples of French Patients at Risk for Aspergillosisspergillus Biomarkers : A Two Centres Approach

Y. Zhao 1, M. Cornet2, M. Brenier-Pinchart2, A. Thiébaut2, C. Saint-Raymond2, B. Camara2, R. Hamidfar2, P. Paderu1, D. S. Perlin1; 1Publ. Hlth. Res. Inst., NJMS, Rutgers Univ., Newark, NJ, 2Ctr. Hosp.ier Univ.ire, Grenoble, France


Background: Azole resistance in Aspergillus fumigatus is increasing. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the prevalence of triazole resistance. We explored the A. fumigatus azole resistance profiles in respiratory samples (RS) from French patients at risk for chronic and invasive aspergillosis. Methods: A total of 26 RS were collected including bronchoalveolar lavage (BAL), bronchial aspirate, sputum, and pleural fluid from 21 patients (5 probable/proven invasive aspergillosis (IA), 1 allergic bronchopulmonary aspergillosis (ABPA), 4 Aspergillus colonization, and 11 controls). Each specimen was evaluated by culture, pan-Aspergillus qPCR (PA), and CYP51A sequencing. Fifteen sera and 7 RS from 12 patients were tested for galactomannan (GM). Results: Aspergillus was detected in 28.5% (2/7) of samples from IA patients by culture vs. 100% by PA qPCR. Silent mutations in A. fumigatus CYP51A at codons D70, T140 and L77 were found from two of these IA samples. The ABPA patient sample was culture and PA PCR positive without CYP51A mutation. All 4 colonized patients were lung transplant recipients, one of whom had cystic fibrosis (CF). Aspergillus sp. was found in 40% (2/5) of samples from colonized patients by culture vs. 100% by PA PCR. The 3 samples that were PA PCR positive and culture negative were from 2 patients with previous positive culture within the last year, one of them has been treated with azoles. Two samples from colonized patients revealed cyp51A mutations. One TR34/L98H in a culture positive sputum from a patient treated with posaconazole and a novel I217T in a culture negative BAL collected from a patient without previous antifungal therapy. No positive result was obtained from controls by either culture or PCR. Moreover, PA PCR showed 100% concordance with GM test where applied. Conclusion: In this series, two cyp51A mutant strains of A. fumigatus were detected in colonized patients, but not in IA patients. Direct molecular detection of resistance markers may facilitate prompt adaptation of appropriate antifungal therapy.


abstract No: 


Full conference title: 

54th Interscience Conference of Antimicrobial Agents and Chemotherapy
    • ICAAC 54th (2014)