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

Shu-Ying Yu,Meng Xiao,Meng-Lan Zhou,Wei Kang,Yao Wang,Ying-Chun Xu,Fanrong Kong,Sharon C.-A Chen,Pei-Yao Jia,Li-Na Guo,Li Zhang,Yanan Zhao,Ying Yuan,Tian-Shu Sun,Ya-Ting Ning

doi:10.3389/fmicb.2020.01672

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 μg/ml), itraconazole (MIC 2 μg/ml), voriconazole (MIC of 4–16 μg/ml), and posaconazole (MIC of 0.5–1 μg/ml). However, MECs for the echinocandin drugs ranged from 0.03–0.25, ≤0.008–0.015, and ≤0.015–0.03 μg/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.

Highlights

MATERIALS AND METHODSInvasive aspergillosis (IA) remains a major invasive fungal infection with serious clinical consequences among immunocompromised patients (Sugui et al, 2014), of which the Aspergillus fumigatus complex is the most common cause
Three patients received prior antifungal therapy including caspofungin in two patients and amphotericin B combined with voriconazole in the other
Phylogenetic analysis based on gene sequences from the combination of the internal transcribed spacer (ITS) region and benA, CaM, and rodlet A (rodA) loci together or each single gene alone showed that the six A. lentulus isolates in our study form a monophyletic cluster with the A. lentulus-type strain, confirming their original identification

Summary

MATERIALS AND METHODS

Invasive aspergillosis (IA) remains a major invasive fungal infection with serious clinical consequences among immunocompromised patients (Sugui et al, 2014), of which the Aspergillus fumigatus complex is the most common cause. Aspergillus lentulus was first described in 2004 as an opportunistic pathogen responsible for fatal infections in four hematopoietic stem cell transplant patients (Balajee et al, 2004; Balajee et al, 2005b) It is a sibling species of A. fumigatus within the A. fumigatus complex but with poor sporulating capacity, leading to diagnostic difficulty (Sugui et al, 2014; Lamoth, 2016). It tends to cause infection associated with higher mortality (over 60%) and poorer clinical outcome compared with that of A. fumigatus (Sugui et al, 2014; Won et al, 2018). The present study is the first to examine the clinical, microbiological, and molecular characteristics of A. lentulus and its infections from China

Ethics Statement

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT