无菌部位侵袭性念珠菌感染的临床特征、药物敏感性及风险因素分析

Clinical characteristics, antifungal sensitivity and risk factors of invasive Candida infection in sterile sites

目的探讨住院患者无菌部位侵袭性念珠菌感染的菌株分布、临床特征、药物敏感性及风险因素。方法跟踪收集116例住院患者无菌部位样本,通过真菌培养、分离与MALDI-TOF MS全自动生物质谱鉴定系统共获80株念珠菌;采用真菌药敏试验检验抗菌药物敏感性,结合患者临床资料分析念珠菌菌株分布、临床特征及药敏特点;对唑类耐药热带念珠菌进行ERG3和ERG11基因测序,以探讨其唑类耐药可能分子机制。结果白色念珠菌是侵袭性念珠菌感染最常见致病菌(45.00%),其次为光滑念珠菌(32.50%)和热带念珠菌(13.75%)。分离标本以尿液(50.00%)为主,分泌物(22.75%)和血液(5.00%)次之。患者年龄、住院时间、相关侵袭性操作及癌症与侵袭性念珠菌感染显著相关(P<0.05)。两性霉素B和5-氟胞嘧啶对念珠菌均有良好的体外抑菌活性。唑类药物对大多数念珠菌体外敏感性较好;而热带念珠菌对唑类药物敏感性普遍较低(54.50%~81.80%),且唑类耐药性热带念珠菌ERG11基因测序显示皆存在2处错义突变(A395T和C461T)。结论白色念珠菌为住院患者侵袭性念珠菌感染主要致病菌;患者特征性自身因素和临床有创性干预应考虑作为侵袭性念珠菌无菌部位感染主要危险因子;临床常用抗真菌药物对非热带念珠菌呈现良好体外抑菌活性,而热带念珠菌ERG11基因突变蛋白产物(Y132F和S154F)或与其唑类耐药相关。

Objective To explore the strain distribution, clinical characteristics, antifungal sensitivity and risk factors of invasive Candida infection in sterile sites of hospitalized patients. Methods Specimens of sterile sites from 116 inpatients were followed up and collected. A total of 80 Candida strains were obtained through fungal culture, separation and MALDI-TOF MS automatic biological mass spectrometry identification system. Antimicrobial susceptibility was tested by fungal drug sensitivity test, and the distribution, clinical characteristics and drug sensitivity characteristics of Candida strains were analyzed based on clinical data of patients;the ERG3 and ERG11 genes of azole-resistant Candida tropicalis were sequenced to investigate a possible molecular mechanism of azole resistance. Results Candida albicans was the most common pathogen of invasive Candida infections(45.00%), followed by Candida glabrata(32.50%) and Candida tropicalis(13.75%). Specimen sources were mainly urine(50.00%), followed by secretions(22.75%) and blood(5.00%). Age of patients, length of hospital stay, related invasive operations and cancer were significantly associated with invasive Candida infections(P<0.05). Amphotericin B and 5-fluorocytosine had strong in vitro antibacterial activities against Candida. Azoles had good sensitivity to most Candida strains in vitro, while the sensitivity of Candida tropicalis to azoles was generally low(form 54.50% to 81.80%), and ERG11 gene sequencing showed that there were two missense mutations(A395 T and C461 T) in azole-resistant Candida tropicalis. Conclusion Candida albicans is predominant in inpatients with invasive Candida infections;patients′distinctive self-factors and clinical invasive intervention should be considered as the main risk factors for invasive Candida infections in sterile sites;antifungal agents commonly used in clinic showed good in vitro antibacterial activity against non-C. tropicalis Candida,while Candida tropicalis ERG11 gene mutant products( Y132F and S154F) may be related to azole resistance.