新疆某医院侵袭性念珠菌感染的菌种分布、药物敏感性及耐药基因初步分析

Preliminary analysis of strains distribution,drug susceptibility characteristics and resistance gene of invasive Candida infections in a hospital in Xinjiang

目的了解新疆某医院侵袭性念珠菌感染的菌株分布、药敏特征,探讨菌株对唑类抗真菌药的耐药机制。方法对分离自临床诊断深部真菌病患者的125株菌行形态学和分子生物学鉴定,分析念珠菌菌种分布特点、对9种抗真菌药的体外敏感性以及对唑类药物耐药菌株行ERG11和PDR1基因测序分析。结果鉴定成功的111株酵母菌株中,分离率在前三位的菌种次为白念珠菌(50.45%)、光滑念珠菌(18.02%)和热带念珠菌(15.32%)。药敏结果显示多数菌株对两性霉素B、5-氟胞嘧啶和棘白菌素类药物敏感,2株光滑念珠菌菌株对棘白菌素类药物耐药。白念珠菌对唑类药物体外敏感性较好,泊沙康唑和伏立康唑对光滑念珠菌和热带念珠菌的体外抑菌活性较低(<60%)。33株唑类耐药念珠菌(6株白念珠菌、14株光滑念珠菌、11株热带念珠菌、1株克柔念珠菌和1株近平滑念珠菌)中有9株存在ERG11基因错义突变,所有唑类耐药光滑念珠菌均存在PDR1基因错义突变。结论侵袭性念珠菌感染的主要致病菌为白念珠菌;棘白菌素类、两性霉素B、5-氟胞嘧啶对念珠菌整体的体外抑菌活性较好,唑类药物对光滑念珠菌和热带念珠菌的抑菌活性较低;念珠菌ERG11和PDR1基因突变可能与唑类耐药相关。

Objective To investigate the distribution of strains,drug susceptibility characteristics,and azole resistance mechanisms of invasive Candida infections in a hospital in Xinjiang.Methods 125 strains isolated from clinically diagnosed invasive fungal infections patients were identified by fungal morphology and molecμlar biology to analyse the distribution of Candida isolates,the susceptibility characteristics of 9 antifungal drugs,and sequencing of ERG11 and PDR1 gene in azole-resistant/non-wide-type(NWT)Candida isolates.Results Of the 111 yeast strains successfully identified,the top three were Candida albicans (50.45%),Candida glabrata(18.02%)and Candida tropicalis(15.32%).Most fungal isolates were susceptible to amphotericin B,5-fluorocytosine and echinocandins,and only two strains of C.glabrata were resistant to echinocandins.Azoles had good in vitro susceptibility to C.albicans,while the antifungal activities of posaconazole and voriconazole against C.glabrata and C.tropicalis were low(<60%).Missense mutations of ERG11 gene was found in 9 of 33 strains of azole-resistant Candida strains(6 C.albicans strains,14 C.glabra strains,11 C.tropicalis strains,1 C.krusei strain and 1 C.parapsilosis strain),and missense mutations of PDR1 gene was found in all azole-resistant C.glabra.strains.Conclusion C.albicans is the predominant causative agent of invasive Candida infections.Echinocandins,amphotericin B,and 5-FC show good in vitro antifungal activity against Candida isolates,and azoles are less effective against C.glabrata and C.tropicalis;azole resistance may be associated with the mutations of ERG11 and PDR1 gene.