Abstract
Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied.Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene.Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V.Conclusions: Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.
Highlights
In the last decade, the taxonomy and nomenclature of the previously morphologically defined genus Aspergillus changed, mainly due to comprehensive molecular phylogenetic studies and the introduction of the single name nomenclature (Samson et al, 2011, 2014; Alastruey-Izquierdo et al, 2013)
Reports on cryptic species within the genus Aspergillus are on the rise (Balajee et al, 2009b; Alastruey-Izquierdo et al, 2013; Negri et al, 2014; Masih et al, 2016) and display variabilities in antifungal susceptibility (Risslegger et al, 2017)
The present study analyzed a large number of isolates (n = 498) collected from Europe, Middle East, South America, North America, and South Asia (Supplementary Table S1 and Supplementary Figure S2) and identified A. terreus (n = 432), A. citrinoterreus (n = 42), A. alabamensis (n = 8), A. hortai (n = 13), A. floccosus (n = 1), and A. neoafricanus (n = 1)
Summary
The taxonomy and nomenclature of the previously morphologically defined genus Aspergillus changed, mainly due to comprehensive molecular phylogenetic studies and the introduction of the single name nomenclature (Samson et al, 2011, 2014; Alastruey-Izquierdo et al, 2013). Samson et al (2011) recognized 13 species in section Terrei: A. terreus sensu stricto (s.s.), A. alabamensis, A. allahabadii, A. ambiguus, A. aureoterreus, A. carneus, A. floccosus, A. hortai, A. microcysticus, A. neoafricanus, A. neoindicus, A. niveus, and A. pseudoterreus. Aspergillus terreus s.s., an important cause of fungal infections in immunocompromised patients, is reported as second or third most common pathogen of invasive aspergillosis (Baddley et al, 2003; Lass-Flörl et al, 2005; Blum et al, 2008). Treatment of infections caused by A. terreus s.s. and other section Terrei species (Walsh et al, 2003; Risslegger et al, 2017) may be difficult because of intrinsic amphotericin B resistance (Sutton et al, 1999; Escribano et al, 2012; Hachem et al, 2014; Risslegger et al, 2017). Azole resistance in A. terreus s.s. and A. fumigatus is associated with mutations
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