重庆市艾滋病患者新型隐球菌临床分离株基因分型和临床特点分析

Genotypes and clinical features of the Cryptococcus neoformans strains isolated from AIDS patients in Chongqing

目的了解重庆市艾滋病患者临床分离新型隐球菌的基因型和药敏谱,分析病例的临床特征,为新型隐球菌感染的诊断和治疗提供依据。方法收集重庆市公共卫生医疗救治中心感染科2017年3月1日—2018年7月31日送检的艾滋病患者行真菌培养的体液标本,对培养分离出的真菌采用商品化真菌鉴定和抗菌药物MIC试剂盒进行菌种鉴定,对两性霉素B、氟胞嘧啶、氟康唑、伊曲康唑和伏立康唑5种抗真菌药物行药敏试验;同时分析患者临床特征与各菌株基因型,并采用多位点序列分型(MLST)进行各菌株的分子遗传学分析。结果1063份体液标本行真菌培养,分离出病原真菌619株,其中189株鉴定为新型隐球菌,占30.5%(189/619)。对患者入院首次分离的54株新型隐球菌进行药敏试验和鉴定分型:1株(1.9%)对伏立康唑耐药,1株(1.9%)对氟胞嘧啶耐药,3株(5.6%)对伊曲康唑耐药,54株对氟康唑和两性霉素B敏感;经鉴定基因型均为VNⅠ型;MLST分型主要为ST5,占85.2%(46/54)。54例艾滋病患者中,男42例,占77.8%(42/54),临床检测指标中脑脊液压力与患者预后显著相关(P<0.05)。结论重庆市艾滋病患者合并新型隐球菌感染较多见,主要为新型隐球菌性脑膜炎,以中年男性为主;其临床分离株对临床常用抗真菌药物较敏感,ST5是其感染的主要克隆系。

Objective To investigate the genotypes and susceptibility profile of the Cryptococcus neoformans strains isolated from AIDS patients in Chongqing area,and analyze the clinical characteristics for improving diagnosis and treatment of C.neoformans infection.Methods The C.neoformans strains were isolated from the AIDS patients treated at Chongqing Public Health Medical Center from March 1,2017 to July 31,2018.The fungal strains were identified with the commercially available fungal identification and antimicrobial MIC Kit.The fungal strains were tested for the susceptibility to amphotericin B,flucytosine,fluconazole,itraconazole,and voriconazole.The clinical characteristics and genotypes of each strain were analyzed.Molecular genetic analysis was conducted for each strain by using multilocus sequence typing(MLST).Results A total of 619 fungal strains were isolated from 1063 body fluid samples,189(30.5%)of which were identified as C.neoformans.Antifungal susceptibility testing and genotyping were performed on the 54 strains of C.neoformans isolated for the first time after admission.The results showed that one strain(1.9%)was resistant to voriconazole,1 strain(1.9%)resistant to flucytosine,3 strains(5.6%)resistant to itraconazole,and 54 strains sensitive to fluconazole and amphotericin B.All genotypes were identified as VN I.The major MLST type was ST5,accounting for 85.2%(46/54).Most(42/54,77.8%)of these AIDS patients were males.CSF pressure was significantly associated with patient outcome(P<0.05).Conclusions Cryptococcal infection is common in AIDS patients in Chongqing,mainly cryptococcal meningitis in middle-aged men.The clinical isolates are susceptible to common antifungal drugs.ST5 is the dominant clone causing infection.