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桉叶油素与抗真菌药物联合应用对血液恶性肿瘤患者白念珠菌分离株的抗生物膜特性。

Anti-biofilm properties of eucalyptol in combination with antifungals against Candida albicans isolates in patients with hematological malignancy.

机构信息

Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Science, Tehran, Iran.

Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Arch Microbiol. 2022 May 4;204(6):295. doi: 10.1007/s00203-022-02911-z.

DOI:10.1007/s00203-022-02911-z
PMID:35508567
Abstract

Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2%) were confirmed for oral candidiasis [mean ± SD age 39 ± 14 years; female 31 (62%) and male 19 (38%)]. C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 µg/mL, 12.55 µg/mL, 0.75 µg/mL and 798 µg/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs.

摘要

口腔念珠菌病是一种由念珠菌属主要引起的真菌感染,是血液恶性肿瘤患者的主要问题。生物膜的形成是念珠菌属毒力和耐药性的一个归因因素。本研究旨在评估口腔白色念珠菌分离株的生物膜形成能力,并评估桉油醇对念珠菌生物膜的抑制活性,单独使用和与抗真菌药物联合使用。从 106 例血液恶性肿瘤患者的口腔中采集样本。通过 PCR 测序鉴定分离出的酵母。然后通过结晶紫染色和 MTT 测定法分析白色念珠菌分离株的生物膜形成能力。根据 CLSI-M-27-A3 方案和棋盘法,分别测试桉油醇、两性霉素 B、伊曲康唑和制霉菌素的最低生物膜抑制浓度(MBIC)以及桉油醇与这些药物的体外相互作用。从 106 例患者中,50 例(47.2%)被确诊为口腔念珠菌病[平均年龄 ± 标准差 39 ± 14 岁;女性 31 例(62%),男性 19 例(38%)]。从 50 例患者中分离出 40 株(80%)白色念珠菌。在 40 株白色念珠菌分离株中,24 株(60%)和 16 株(40%)为中度和弱生物膜生产者。两性霉素 B、伊曲康唑、制霉菌素和桉油醇的几何平均 MBIC 分别为 3.93 µg/mL、12.55 µg/mL、0.75 µg/mL 和 798 µg/mL。桉油醇与两性霉素 B、伊曲康唑和制霉菌素联合使用时,对 12.5%、10%和 22.5%的分离株表现出协同作用。桉油醇单独或与抗真菌药物联合使用时,对白色念珠菌生物膜表现出良好的活性。

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