云南省艾滋病患者新生隐球菌药物敏感性与临床分析

Drug susceptibility and clinical analysis of Cryptococcus neoformans from patients with acquired immunodeficiency syndrome in Yunnan province

目的了解云南省艾滋病患者中新生隐球菌病的病原分离部位、耐药性及临床治疗效果。方法对2010年1月至2020年12月临床总共分离的424株新生隐球菌,用VITEK2 Compact全自动微生物分析仪鉴定菌种,ATB FUNGUS 3检测5种抗真菌药物的敏感性,并对临床资料进行分析。结果424株新生隐球菌以脑脊液检出比例最高,占62.50%(265/424);血液次之,占30.90%(131/424);第三是痰液,占2.83%(12/424)。424株新生隐球菌对唑类抗真菌药物伊曲康唑和伏立康唑MIC范围均≤2μg/mL,多烯类的两性霉素B MIC范围≤4μg/mL,氟康唑及5-氟胞嘧啶的MIC范围≤64μg/mL。对两性霉素B、氟康唑、5-氟胞嘧啶的敏感性分别为95.28%(404/424)、80.66%(342/424)、75.71%(321/424)。5种抗真菌药物的流行病学折点分别为:5-氟胞嘧啶和氟康唑16μg/mL;两性霉素B、伊曲康唑和伏立康唑0.5μg/mL。结论新生隐球菌对两性霉素B的敏感性较好,而氟康唑及5-氟胞嘧啶在多年的临床用药过程中已慢慢出现非敏感菌株,伊曲康唑和伏立康唑MIC范围≤2μg/mL。新生隐球菌药敏试验结果为临床医生用药提供参考依据。新生隐球菌病治疗首选两性霉素B与5-氟胞嘧啶联合治疗。隐球菌作为临床重要的致病真菌,实验室及临床均应给予高度重视。

Objective To investigate the distribution,drug resistance and clinical treatment effect of Cryptococcus neoformans(C.neoformans)isolated from patients with acquired immunodeficiency syndrom(AIDS)in Yunnan province.Methods A total of 424 strains of C.neoformans isolated from AIDS patients in Yunnan Infectious Diseases Hospital from January 2010 to December 2020 were identified by VITEK Compact automatic microorganism analyzer,and the sensitivity of 5 antifungal drugs was detected by ATB FUNGUS 3.The clinical data were alalyzed.Results The highest proportion of 424 strains of C.neoformans was detected in cerebrospinal fluid,62.50%(265/424).Blood was the second,accounting for 30.90%(131/424).The third was sputum,accounting for 2.83%(12/424).The MIC for azole(except fluconazole)to C.neoformans was≤2μg/mL,the MIC for amphotericin B of polyene was≤4μg/mL,and the MIC for fluconazole and 5-fluorocytosine was≤64μg/mL.The sensitivity rate to amphotericin B,fluconazole and 5-fluorocytosine was 95.28%(404/424),80.66%(342/424)and 75.71%(321/424),respectively.The epidemiologic cutoff value of 5-fluorocytosine and fluconazole was 16μg/mL,and the ECV of amphotericin B itraconazole and voriconazole was 0.5μg/mL.Conclusion Cryptococcus neoformances is more sensitive to amphotericin B,while fluconazole and 5-flucytosine have gradually emerged as non-sensitive strains in the clinical medication process for so many years,and the MIC range of itraconazole and voriconazole is≤2μg/mL.The results of drug sensitivity test of C.neoformans provide reference for clinicians to select drugs.Combined amphotericin B with 5-fluorocytosine was the first choice of treatment of C.neoformans.Cryptococcus,as an important pathogenic fungus in clinic,should be valued highly by laboratory and clinic.