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侵袭性曲霉菌分离株的流行病学特征:形态学、药敏性及唑类药物靶点的突变

Epidemiological characteristics of invasive Aspergillus isolates: Morphology, drug susceptibility, and mutations in azole drug targets.

作者信息

Zhang Wei, Zhang Hongxia, Zhan Minghua, Jing Ran, Wang Xinsheng, Zhang Zhihua

机构信息

Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, People's Republic of China.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, People's Republic of China.

出版信息

J Infect Public Health. 2025 Jan;18(1):102612. doi: 10.1016/j.jiph.2024.102612. Epub 2024 Dec 2.

DOI:10.1016/j.jiph.2024.102612
PMID:39637619
Abstract

BACKGROUND

The global epidemiology of aspergillosis varies and is influenced by various factors. To elucidate the disease burden and identify effective control strategies, the epidemiological characteristics of Aspergillus infections have to be investigated. The aim of this study was to assess the epidemiological characteristics of various Aspergillus species, including their morphological features, species identification, and in vitro susceptibility to nine antifungal agents in a large tertiary hospital in northern China.

METHODS

Ninety-five clinical isolates of Aspergillus were collected from patients. Aspergillus species identification was performed using conventional morphological methods, MALDI-TOF MS, and gene sequencing. In vitro susceptibility to nine antifungal agents was evaluated using the Sensititre YeastOne system. Target genes (cyp51A and cyp51b) of A. tubinazole were sequenced using the Sanger method.

RESULTS

Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, Aspergillus tubingensis, and Aspergillus terreus were the most common isolated species. Rare species included Aspergillus tamarii, Aspergillus usamil, Aspergillus versicolor, Aspergillus udagawae, Aspergillus lentulus, Aspergillus sydowii, and Aspergillus quadrilineatus. Pulmonary infections accounted for 86.3 % (82/95) of collected cases, and the in-hospital mortality rate was 22.1 %. The median minimum inhibitory concentration (MIC) range of amphotericin B was 1.5-4 mg/L. The MIC range of triazoles against Aspergillus species, excluding Aspergillus udagawae and Aspergillus lentulus, was 0.12-0.5 mg/L. The median minimum effective concentration range of echinocandins was < 0.008-0.03 mg/L. Non-wild-type resistance to amphotericin B was observed in 29.6 % (16/54) of Aspergillus fumigatus isolates, and non-wild-type resistance to voriconazole was observed in 11.1 % (1/9) of Aspergillus tubingensis isolates. Moreover, CYP51A and CYP51b of Aspergillus tabinensis had 2-29 and 10-13 nucleotide mutations, respectively.

CONCLUSION

Patients with non- Aspergillus fumigatus infection accounted for 43.2 %. The T256A amino acid substitution in CYP51A of Aspergillus tabinensis did not lead to increased azole drug MICs.

摘要

背景

曲霉病的全球流行病学情况各异,且受多种因素影响。为阐明疾病负担并确定有效的控制策略,必须对曲霉感染的流行病学特征进行调查。本研究旨在评估中国北方一家大型三级医院中各种曲霉菌种的流行病学特征,包括其形态特征、菌种鉴定以及对九种抗真菌药物的体外敏感性。

方法

从患者中收集了95株曲霉临床分离株。采用传统形态学方法、基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)和基因测序进行曲霉菌种鉴定。使用Sensititre YeastOne系统评估对九种抗真菌药物的体外敏感性。采用桑格法对土曲霉的靶基因(cyp51A和cyp51b)进行测序。

结果

烟曲霉、黑曲霉、黄曲霉、土曲霉和构巢曲霉是最常见的分离菌种。罕见菌种包括溜曲霉、乌萨米曲霉、杂色曲霉、uda曲霉菌、勒图曲霉、栖土曲霉和四线曲霉。肺部感染占收集病例的86.3%(82/95),院内死亡率为22.1%。两性霉素B的中位最低抑菌浓度(MIC)范围为1.5 - 4mg/L。三唑类药物对除uda曲霉菌和勒图曲霉之外的曲霉菌种的MIC范围为0.12 - 0.5mg/L。棘白菌素类的中位最低有效浓度范围为<0.008 - 0.03mg/L。在29.6%(16/54)的烟曲霉分离株中观察到对两性霉素B的非野生型耐药,在11.1%(1/9)的土曲霉分离株中观察到对伏立康唑的非野生型耐药。此外,土曲霉的CYP51A和CYP51b分别有2 - 29个和10 - 13个核苷酸突变。

结论

非烟曲霉感染患者占43.2%。土曲霉CYP51A中的T256A氨基酸替换并未导致唑类药物MIC升高。

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