阿尼芬净对血流感染光滑念珠菌生物膜的拮抗作用

Antagonistic effect of anidulafungin on Candida glabrata biofilm with bloodstream infection

  • 摘要:
    目的 光滑念珠菌生物膜的形成增加了其对抗真菌药物的耐药性, 是重要的毒力因子之一。阿尼芬净是棘白菌素类抗真菌药物, 国内对此药物研究甚少。本研究探究阿尼芬净对光滑念珠菌生物膜形成的抑制作用, 以及对成熟生物膜的根除作用, 为念珠菌血症的临床治疗提供帮助。
    方法 回顾首都医科大学附属北京朝阳医院2017年1月-2024年1月血源性光滑念珠菌感染病例20例, 分析其临床特征。收集光滑念珠菌临床菌株, 使用结晶紫染色法检测生物膜形成能力。用YeastOne plate真菌药敏板测定光滑念珠菌的最小抑菌浓度(MIC)。测定阿尼芬净对光滑念珠菌的最小生物膜抑制浓度(MBIC)和最小生物膜根除浓度(MBEC), 并分析阿尼芬净处理对生物膜的作用影响。
    结果 患者年龄(66.67±19.14)岁;住院时长(32.00±32.57)d;有一种及以上的基础疾病90.00%, 入住重症监护病房(ICU)45.00%, 患者有侵袭性操作经历95.00%;真菌-D葡聚糖试验阳性率为50.00%。同时检测这20株光滑念珠菌的生物膜的形成能力, 具有强、中、弱形成能力的菌株分别占45.00%、35.00%和20.00%。阿尼芬净对光滑念珠菌的MIC均≤0.03 μg/ml, MBIC在0.02~0.06 μg/ml, MBEC>32 μg/ml占70.00%。
    结论 阿尼芬净能有效抑制光滑念珠菌生物膜的形成, 但对成熟生物膜的根除效果有限。若光滑念珠菌在体内形成成熟的生物膜, 可能会导致治疗效果不佳。寻找能够有效抑制光滑念珠菌生物膜形成并根除其成熟生物膜的新型抗真菌药物至关重要。

     

    Abstract:
    OBJECTIVE The formation of Candida glabrata biofilm increases its resistance to antifungal drugs and is one of the important virulence factors. Anidulafungin is an echinocandin antifungal drug, and there is limited research on this drug in China. This study investigated the inhibitory effect of anidulafungin on the formation of C. glabrata biofilm and its eradication effect on mature biofilms, and provided assistance for the clinical treatment of candidemia.
    METHODS A retrospective analysis was conducted on 20 cases of bloodstream infection caused by C. glabrata in Beijing Chaoyang Hospital, Capital Medical University, from Jan. 2017 to Jan. 2024. Clinical characteristics of the patients were analyzed. Clinical strains of C. glabrata were collected, and the biofilm formation ability was detected through the crystal violet staining method. The minimum inhibitory concentration (MIC) of C. glabrata was determined with the YeastOne plate fungal susceptibility panel. The minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) of anidulafungin against C. glabrata were measured, and the effect of anidulafungin treatment on biofilms was analyzed.
    RESULTS The patients′ age was (66.67±19.14) years. The length of hospital stay was (32.00±32.57) days. In addition, 90.00% of patients had one or more underlying diseases, 45.00% were admitted to the intensive care unit (ICU), and 95.00% had undergone invasive procedures. The positivity rate of fungal (1, 3)-β-D-glucan test was 50.00%. The biofilm formation ability of these 20 C. glabrata strains was also tested, with 45.00%, 35.00% and 20.00% of the strains showing strong, moderate and weak biofilm formation abilities, respectively. The MIC of anidulafungin against C. glabrata was ≤0.03 μg/ml, the MBIC ranged from 0.02 to 0.06 μg/ml, and MBEC >32 μg/ml accounted for 70.00%.
    CONCLUSIONS Anidulafungin can effectively inhibit the formation of C. glabrata biofilm but has limited eradication effect on mature biofilms. If C. glabrata forms mature biofilms in the body, it may lead to poor treatment outcomes. It is crucial to search for new antifungal drugs that can effectively inhibit the formation of C. glabrata biofilm and eradicate mature biofilms.

     

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