Low prevalence of resistance to azoles in Aspergillus fumigatus in a French cohort of patients treated for haematological malignancies

Alexandre Alanio (1) , E. Sitterle (1) , M. Liance (1, 2) , C. Farrugia (1, 2) , F. Foulet (1) , F. Botterel (1, 2) , Y. Hicheri (3) , C. Cordonnier (3, 2) , J.-M. Costa (3, 4) , S. Bretagne (5, 6, 2)

1 Laboratoire de Parasitologie-Mycologie
2 BIPAR - Biologie moléculaire et immunologie parasitaires et fongiques
3 Service d'hématologie clinique
4 Laboratoire CERBA
5 CNRMA - Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire
6 Hôpital Henri Mondor

OBJECTIVES: An increase in invasive aspergillosis (IA) due to azole-resistant Aspergillus fumigatus isolates has been reported for 10 years. Our study aimed to estimate the prevalence of azole resistance in isolates prospectively collected in patients with haematological diseases. METHODS: One hundred and eighteen isolates were collected from 89 consecutive patients over 4 years. Fifty-one patients had proven or probable IA. Species identification was ascertained based on β-tubulin gene sequencing. The MICs of azole drugs were determined using Etest(®), and the cyp51A gene and its promoter were sequenced to detect mutations. RESULTS: All isolates were identified as A. fumigatus and all of them but one had itraconazole and voriconazole MICs of ≤ 2 mg/L and posaconazole MICs of ≤ 0.25 mg/L. An isolate for which the itraconazole MIC was high (itraconazole MIC = 16 mg/L; voriconazole MIC = 0.38 mg/L; and posaconazole MIC = 0.25 mg/L) was recovered from a patient naive to azole treatment and had a new G432S substitution. To establish whether this mutation existed in other isolates, the 1426-2025 bp cyp51A locus was sequenced for all. G432S was not found. CONCLUSIONS: In A. fumigatus, the prevalence of azole resistance is currently low in the haematological population in the Paris area. Surveillance programmes for azole resistance to adapt antifungal treatments are warranted for clinical isolates of A. fumigatus.

Keywords: Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Pyrimidines; Triazoles; Tubulin; voriconazole; Hematologic Neoplasms; Female; France; Fungal Proteins; Adolescent; Adult; Aged; 80 and over; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Azoles; Cohort Studies; Cytochrome P-450 Enzyme System; Drug Resistance; Fungal; Humans

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Human health and pathology; Hematology

Alexandre Alanio, E. Sitterle, M. Liance, C. Farrugia, F. Foulet, et al.. Low prevalence of resistance to azoles in Aspergillus fumigatus in a French cohort of patients treated for haematological malignancies. Journal of Antimicrobial Chemotherapy, 2011, 66 (2), pp.371 - 374. ⟨10.1093/jac/dkq450⟩. ⟨pasteur-01405258⟩