Aspergillus Species in Lower Respiratory Tract of Hospitalized Patients from Shanghai, China: Species Diversity and Emerging Azole Resistance

Xu, Yuan; Chen, Min; Zhu, Junhao; Ende, Bert Gerrits van den; Chen, Amanda Juan; Al‐Hatmi, Abdullah M. S.; Li, Li; Zhang, Qiangqiang; Xu, Jianping; Liao, Wanqing; Chen, Yuchong

doi:10.2147/idr.s281288

Cited by 10 publications

(12 citation statements)

References 73 publications

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“…This study suggests that the AMB susceptibility to Aspergillus spp. in local China would be similar to other studies (34)(35)(36), which should be under close surveillance. Resistance to AMB is usually caused by decreased ergosterol or changed lipids of the target in plasma membrane due to alterations of ergosterol biosynthetic pathways which lead to decreased abilities to binding AMB (37), germination of conidia by UV irradiation (38), and mutations of genes encoding sphingolipids FEN1 and SUR4 (39).…”

Section: Discussionsupporting

confidence: 85%

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Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

Wang

Zhang

Zhou

et al. 2022

Front. Public Health

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BackgroundThis study aimed to investigate the Aspergillus species distribution, antifungal sensitivities, clinical characteristics, and risk factors of patients with invasive aspergillosis (IA) in a tertiary teaching hospital in Anhui Province.MethodsIn the present study, 156 Aspergillus isolates were collected from patients admitted to a 2,800-bed comprehensive hospital between January 2019 and April 2021. The epidemiology of Aspergillus species was well-examined, and its antifungal susceptibility was specifically measured by the microbroth dilution method. The risk factors of patients with IA were documented and analyzed intensively. In addition, gene sequencing was employed to determine gene mutations of cytochrome P450 14-α sterol demethylase-Aspergillus (cyp51A) associated with azole resistance among Aspergillus fumigatus.ResultsThe Aspergillus species distribution was dominated by A. fumigatus (56.41%), Aspergillus flavus (20.51%), and Aspergillus niger (15.38%) locally. In particular, all Aspergillus species showed very low minimum inhibitory concentrations (MICs, ≤ 0.5 μg/ml) for azoles and echinocandins, slightly high MICs (1.66–2.91 μg/ml) for amphotericin B, and exceptionally high MICs (>64 μg/ml) for flucytosine. Azole-resistant rate of Aspergillus species in this local region reached up to 5.79%. Correlation analyses of multiple antifungals indicate a significant MIC relevance between isavuconazole and voriconazole (Pearson correlation coefficient was 0.81, P < 0.0001). The clinical risk factors for patients with IA were found primarily to be pulmonary diseases (P = 0.007) and patients' age (P < 0.001). Notably, three mutant loci (TR46/Y121F/T289A) of the cyp51A gene were identified in azole-resistant A. fumigatus.ConclusionsThe Aspergillus species emerged increasingly, of which A. fumigatus and A. flavus remained the main pathogens for invasive Aspergillus infections in the local region. The vast majority of Aspergillus species exhibited good susceptibility to all the antifungals, except flucytosine. The local occurrence of azole-resistant Aspergillus species grew gradually and needed monitoring in time. Pulmonary diseases and age were likely considered as highly associated risk factors for IA. To our knowledge, the clinically isolated azole-resistant A. fumigatus with TR46/Y121F/T289A mutations identified here were rarely reported in the area of China.

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Section: Discussionsupporting

confidence: 85%

“…The data from the global antifungal surveillance program showed that 5.79% of A. fumigatus elevated MICs for one or more azoles (21). The reported frequency of azole resistance differs remarkably between countries/regions, and the antifungal resistance makes the diagnosis and treatment of aspergillosis more complicated (42) (8,23,34).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

Wang

Zhang

Zhou

et al. 2022

Front. Public Health

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“…was more effective than triazoles against A. fumigatus (Xu et al, 2020). Therefore, AMB appears to be the most active antifungal agent against A. fumigatus.…”

Section: Discussionmentioning

confidence: 91%

A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for Aspergillus spp. and Proposed Epidemiological Cutoff Values for Aspergillus fumigatus and Aspergillus flavus: A Study in a Tertiary Hospital in China

et al. 2021

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The emergence of resistant Aspergillus spp. is increasing worldwide. Long-term susceptibility surveillance for clinically isolated Aspergillus spp. strains is warranted for understanding the dynamic change in susceptibility and monitoring the emergence of resistance. Additionally, neither clinical breakpoints (CBPs) nor epidemiological cutoff values (ECVs) for Aspergillus spp. in China have been established. In this study, we performed a 20-year antifungal susceptibility surveillance for 706 isolates of Aspergillus spp. in a clinical laboratory at Peking University First Hospital from 1999 to 2019; and in vitro antifungal susceptibility to triazoles, caspofungin, and amphotericin B was determined by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. It was observed that Aspergillus fumigatus was the most common species, followed by Aspergillus flavus and Aspergillus terreus. Forty isolates (5.7%), including A. fumigatus, A. flavus, A. terreus, Aspergillus niger, and Aspergillus nidulans, were classified as non-wild type (non-WT). Importantly, multidrug resistance was observed among A. flavus, A. terreus, and A. niger isolates. Cyp51A mutations were characterized for 19 non-WT A. fumigatus isolates, and TR34/L98H/S297T/F495I was the most prevalent mutation during the 20-year surveillance period. The overall resistance trend of A. fumigatus increased over 20 years in China. Furthermore, based on ECV establishment principles, proposed ECVs for A. fumigatus and A. flavus were established using gathered minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) data. Consequently, all the proposed ECVs were identical to the CLSI ECVs, with the exception of itraconazole against A. flavus, resulting in a decrease in the non-WT rate from 6.0 to 0.6%.

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“…A. oryzae var. effusus has been reported as a cause of keratitis [6] and has been isolated from the lower respiratory tract of hospitalized patients [85]. In 2019, one case of A. caelatus airway colonization in a chronic obstructive pulmonary disease patient was reported in Colombia [86].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Identification and Antifungal Susceptibility of Clinical Isolates of Aspergillus Section Flavi from Three French Hospitals

Djenontin,

Costa,

Mousavi

et al. 2023

Microorganisms

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(1) Background: Aspergillus flavus is a cosmopolitan mold with medical, veterinary, and agronomic concerns. Its morphological similarity to other cryptic species of the Flavi section requires molecular identification techniques that are not routinely performed. For clinical isolates of Aspergillus section Flavi, we present the molecular identification, susceptibility to six antifungal agents, and clinical context of source patients. (2) Methods: One hundred forty fungal clinical isolates were included in the study. These isolates, recovered over a 15-year period (2001–2015), were identified based on their morphological characteristics as belonging to section Flavi. After the subculture, sequencing of a part of the β-tubulin and calmodulin genes was performed, and resistance to azole antifungals was screened on agar plates containing itraconazole and voriconazole. Minimum inhibitory concentrations were determined for 120 isolates by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. (3) Results: Partial β-tubulin and calmodulin sequences analysis showed that 138/140 isolates were A. flavus sensu stricto, 1 isolate was A. parasiticus/sojae, and 1 was A. nomiae. Many of the isolates came from samples collected in the context of respiratory tract colonization. Among probable or proven aspergillosis, respiratory infections were the most frequent, followed by ENT infections. Antifungal susceptibility testing was available for isolates (n = 120, all A. flavus ss) from one hospital. The MIC range (geometric mean MIC) in mg/L was 0.5–8 (0.77), 0.5–8 (1.03), 0.125–2 (0.25), 0.03–2 (0.22), 0.25–8 (1.91), and 0.03–0.125 (0.061) for voriconazole, isavuconazole, itraconazole, posaconazole, amphotericin B, and caspofungin, respectively. Two (1.67%) isolates showed resistance to isavuconazole according to current EUCAST breakpoints with MICs at 8 mg/L for isavuconazole and voriconazole. One of these two isolates was also resistant to itraconazole with MIC at 2 mg/L. (4) Conclusions: The present characterization of a large collection of Aspergillus belonging to the Flavi section confirmed that A. flavus ss is the predominant species. It is mainly implicated in respiratory and ENT infections. The emergence of resistance highlights the need to perform susceptibility tests on section Flavi isolates.

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Aspergillus Species in Lower Respiratory Tract of Hospitalized Patients from Shanghai, China: Species Diversity and Emerging Azole Resistance

Cited by 10 publications

References 73 publications

Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for Aspergillus spp. and Proposed Epidemiological Cutoff Values for Aspergillus fumigatus and Aspergillus flavus: A Study in a Tertiary Hospital in China

The Molecular Identification and Antifungal Susceptibility of Clinical Isolates of Aspergillus Section Flavi from Three French Hospitals

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