Clinical and Microbiological Characterization of Invasive Pulmonary Aspergillosis Caused by Aspergillus lentulus in China

Invasive aspergillosis (IA) due toAspergillus lentulusis associated with high mortality. In this study, we investigated the clinical and microbiological characteristics of 6 fatal cases of proven or probable IA caused byA. lentulusin China. Underlying immunosuppression, prior antifungal exposure, and intensive care unit (ICU) hospitalization were important risk factors for invasiveA. lentulusinfection. Phenotypic differences were observed forA. lentulusisolates including slower growth, reduced sporulation, and inability to grow at 48 degrees C, compared withAspergillus fumigatus complex. ITS sequencing was unable to distinguishA. lentulusfromA. fumigatus, but sequencing of thebenA,CaM, androd Aloci enabled reliable distinction of these closely related species. Phylogenetic analysis further confirmed that the ITS region had little variation within theAspergillussection Fumigati while thebenAgene offered the highest intraspecific discrimination. Microsatellite typing results revealed that only loci on chromosomes 1, 3, 5, and 6b generated detectable amplicons for identification. AllA. lentulusisolates showedin vitroresistance to multiple antifungal drugs including amphotericin B (MIC range 4 to 8 mu g/ml), itraconazole (MIC 2 mu g/ml), voriconazole (MIC of 4-16 mu g/ml), and posaconazole (MIC of 0.5-1 mu g/ml). However, MECs for the echinocandin drugs ranged from 0.03-0.25, <= 0.008-0.015, and <= 0.015-0.03 mu g/ml for caspofungin, micafungin, and anidulafungin, respectively.A. lentulusis an emerging fungal pathogen in China, causing fatal disease, and clinicians as well as laboratories should be alert to their increasing presence.