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

ABSTRACT: Invasive aspergillosis (IA) due to Aspergillus lentulus is associated with high mortality. In this study, we investigated the clinical and microbiological characteristics of 6 fatal cases of proven or probable IA caused by A. lentulus in China. Underlying immunosuppression, prior antifungal exposure, and intensive care unit (ICU) hospitalization were important risk factors for invasive A. lentulus infection. Phenotypic differences were observed for A. lentulus isolates including slower growth, reduced sporulation, and inability to grow at 48°C, compared with Aspergillus fumigatus complex. ITS sequencing was unable to distinguish A. lentulus from A. fumigatus, but sequencing of the benA, CaM, and rod A loci enabled reliable distinction of these closely related species. Phylogenetic analysis further confirmed that the ITS region had little variation within the Aspergillus section Fumigati while the benA gene offered the highest intraspecific discrimination. Microsatellite typing results revealed that only loci on chromosomes 1, 3, 5, and 6b generated detectable amplicons for identification. All A. lentulus isolates showed in vitro resistance to multiple antifungal drugs including amphotericin B (MIC range 4 to 8 ?g/ml), itraconazole (MIC 2 ?g/ml), voriconazole (MIC of 4-16 ?g/ml), and posaconazole (MIC of 0.5-1 ?g/ml). However, MECs for the echinocandin drugs ranged from 0.03-0.25, ?0.008-0.015, and ?0.015-0.03 ?g/ml for caspofungin, micafungin, and anidulafungin, respectively. A. lentulus is an emerging fungal pathogen in China, causing fatal disease, and clinicians as well as laboratories should be alert to their increasing presence.

SUBMITTER: Yu SY

PROVIDER: S-EPMC7399017 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Yu Shu-Ying SY Guo Li-Na LN Xiao Meng M Zhou Meng-Lan ML Yuan Ying Y Wang Yao Y Zhang Li L Sun Tian-Shu TS Ning Ya-Ting YT Jia Pei-Yao PY Kang Wei W Kong Fanrong F Chen Sharon C-A SC Zhao Yanan Y Xu Ying-Chun YC

Frontiers in microbiology 20200728

Invasive aspergillosis (IA) due to Aspergillus lentulus is associated with high mortality. In this study, we investigated the clinical and microbiological characteristics of 6 fatal cases of proven or probable IA caused by A. lentulus in China. Underlying immunosuppression, prior antifungal exposure, and intensive care unit (ICU) hospitalization were important risk factors for invasive A. lentulus infection. Phenotypic differences were observed for A. lentulus isolate ...[more]

PMID: 32849346

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Project description:With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non-fumigatus Aspergillus spp.-namely A. flavus, A. terreus, A. niger and A. nidulans-including diagnostic and therapeutic differences and similarities to A. fumigatus. A. flavus is the second most common Aspergillus spp. isolated in patients with IA and the predominant species in subtropical regions. Treatment is complicated by its intrinsic resistance against amphotericin B (AmB) and high minimum inhibitory concentrations (MIC) for voriconazole. A. nidulans has been frequently isolated in patients with long-term immunosuppression, mostly in patients with primary immunodeficiencies such as chronic granulomatous disease. It has been reported to disseminate more often than other Aspergillus spp. Innate resistance against AmB has been suggested but not yet proven, while MICs seem to be elevated. A. niger is more frequently reported in less severe infections such as otomycosis. Triazoles exhibit varying MICs and are therefore not strictly recommended as first-line treatment for IA caused by A. niger, while patient outcome seems to be more favorable when compared to IA due to other Aspergillus species. A. terreus-related infections have been reported increasingly as the cause of acute and chronic aspergillosis. A recent prospective international multicenter surveillance study showed Spain, Austria, and Israel to be the countries with the highest density of A. terreus species complex isolates collected. This species complex seems to cause dissemination more often and is intrinsically resistant to AmB. Non-fumigatus aspergillosis is difficult to manage due to complex patient histories, varying infection sites and potential intrinsic resistances to antifungals. Future investigational efforts should aim at amplifying the knowledge on specific diagnostic measures and their on-site availability, as well as defining optimal treatment strategies and outcomes of non-fumigatus aspergillosis.

Dataset Information

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

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Clinical and Microbiological Characterization of Invasive Pulmonary Aspergillosis Caused by <i>Aspergillus lentulus</i> in China.

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