Low prevalence of resistance to azoles in Aspergillus fumigatus in a French cohort of patients treated for haematological malignancies.
OBJECTIVE
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.
Laboratoire de Parasitologie-Mycologie, Groupe hospitalier Chenevier-Mondor, Assitance Publique-Hôpitaux de Paris, Créteil, France.
Alexandre
A
Alanio
Emilie
E
Sitterlé
Martine
M
Liance
Cécile
C
Farrugia
Françoise
F
Foulet
Françoise
F
Botterel
Yosr
Y
Hicheri
Catherine
C
Cordonnier
Jean-Marc
JM
Costa
Stéphane
S
Bretagne
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001393:Azoles / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics; D005260:Female; D005602:France; D005656:Fungal Proteins / Q000235:genetics; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D011743:Pyrimidines / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D014404:Tubulin / Q000235:genetics; D065819:Voriconazole
D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D011743:Pyrimidines; D014230:Triazoles; D014404:Tubulin; D017964:Itraconazole; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole