Is azole resistance in Aspergillus fumigatus a problem in Spain? Antimicrob Agents Chemother 57:2815–2820

Aspergillus fumigatus complex comprises A. fumigatus and other morphologically indistinguishable cryptic species. We retro-spectively studied 362 A. fumigatus complex isolates (353 samples) from 150 patients with proven or probable invasive aspergil-losis or aspergilloma (2, 121, and 6 samples, respectively) admitted to the hospital from 1999 to 2011. Isolates were identified using the-tubulin gene, and only 1 isolate per species found in each sample was selected. Antifungal susceptibility to azoles was determined using the CLSI M38-A2 procedure. Isolates were considered resistant if they showed anMIC above the breakpoints for itraconazole, voriconazole, or posaconazole (>2,>2, or>0.5g/ml). Most of the samples yielded only 1 species (A. fumiga-tus [n 335], A. novofumigatus [n 4], A. lentulus [n 3], A. viridinutans [n 1], and Neosartorya udagawae [n 1]). The remaining samples yielded a combination of 2 species. Most of the patients were infected by a single species (A. fumigatus [n 143] or A. lentulus [n 2]). The remaining 5 patients were coinfected with multiple A. fumigatus complex species, although A. fumigatuswas always involved; 4 of the 5 patients were diagnosed in 2009 or later. Cryptic species were less susceptible than A. fumigatus. The frequency of resistance among A. fumigatus complex and A. fumigatus to itraconazole, voriconazole, and po-saconazole was 2.5 and 0.3%, 3.1 and 0.3%, and 4.2 and 1.8%, respectively, in the per-isolate analysis and 1.3 and 0.7%, 2.6 and 0.7%, and 6 and 4 % in the per-patient analysis. Only 1 of the 6 A. fumigatus isolates in which the cyp51A gene was sequenced had a mutation at position G448. The proportion of patients infected by azole-resistant A. fumigatus isolates was low. Invasive aspergillosis (IA), an opportunistic infection that affectspatients with different degrees of immunosuppression (1–7), i