摘要
目的探究经宏基因组二代测序技术确诊的非人类免疫缺陷病毒(HIV)耶氏肺孢子菌重症肺炎患者的临床特征,对治疗的药物进行合理性分析。方法回顾性分析2021年1月-2023年12月在东南大学附属中大医院重症监护病房住院且经支气管肺泡灌洗液和(或)血二代测序结合临床确诊的16例非HIV耶氏肺孢子菌重症肺炎患者的临床资料,分析基础疾病、实验室检查指标、影像学表现、药物治疗及转归等情况。结果16例非HIV耶氏肺孢子菌重症肺炎患者中,男性7例,女性9例,年龄29~77岁。急性生理和慢性健康(APACHE)Ⅱ评分均值为(19.90±8.40)分,序贯器官衰竭(SOFA)评分中位数6.50(4.80)分;大部分以咳嗽、咳痰、胸闷气短、发热等症状起病;10例有自身免疫性基础疾病,肿瘤4例,1例为肾移植术后;住院前使用激素史11例,化疗或使用免疫抑制剂9例;入ICU后(首次检查结果)总淋巴细胞计数中位数0.38(0.54)×10^(9)/L,C-反应蛋白为(111.51±81.40)mg/L,CD_(4)^(+)T细胞计数<200个/μl为60.00%(9/15),CD_(4)^(+)T细胞计数中位数为112.30(230.52)个/μl,(1,3)-β-D葡聚糖>200pg/ml及乳酸脱氢酶>250U/L均为10例,白蛋白为(27.08±4.04)g/L;16例患者中宏基因组二代测序技术检出巨细胞和(或)EB病毒为9例(56.25%),13例检测血浆中巨细胞病毒DNA和(或)EB病毒DNA中8例为阳性;在磺胺甲噁唑/甲氧苄啶联合(不联合)棘白菌素治疗的基础上,75.00%(12/16)患者使用了抗病毒药物,93.75%(15/16)患者使用激素,56.25%(9/16)患者使用丙种球蛋白,62.50%(10/16)患者使用胸腺肽,93.75%(15/16)患者经验性或目标性使用其他抗菌药物,经治疗后9例(56.25%)好转。结论非HIV耶氏肺孢子菌重症肺炎患者的自身免疫性基础疾病较多,以混合感染为主,病死率较高,宏基因组二代测序技术可为该类感染提供较好的病原学证据,除抗耶氏肺孢子菌治疗的磺胺甲噁唑/甲氧苄啶及棘白菌素类药物外,激素、丙种球蛋白、胸腺肽及其他抗菌药物的使用应个体化,需更多的临床数据支持。
OBJECTIVE To investigate clinical characteristics of patients with non-HIV Pneumocystis jiroveci(PJ)severe pneumonia confirmed by metagenomic next-generation sequencing,and to analyze the rationality of the drugs used for treatment.METHOD We retrospectively analyzed the clinical data of 16 patients with non-HIV Pneumocystis jirovecii severe pneumonia who were hospitalized in the intensive care unit of Zhongda Hospital Affiliated to Southeast University and diagnosed by metagenomic next-generation sequencing on bronchoalveolar lavage fluid and/or blood in combination with clinically confirmed diagnosis from Jan.2021 to Dec.2023,and the underlying diseases,clinical data,laboratory test indices,imaging manifestations,drug treatment and regression were also analyzed.RESULTS Among the 16 PJP patients,there were seven men and nine women,aged 29-77 years.Mean APACHE Ⅱ score was(19.90±8.40),and median SOFA score was 6.50(4.80)points.Most of them started with symptoms such as coughing,coughing up sputum,chest tightness and shortness of breath,and fever.Totally 10 patients had autoimmune underlying diseases,4 patients had tumors and 1 patient was post kidney transplantation.Totally 11 patients had a history of hormone use prior to hospitalization,and 9 patients had chemotherapy or use of immunosuppressants.After ICU admission(first results),median total lymphocyte count was 0.38(0.54)×10^(9)/L,mean C-reactive protein value was(111.51±81.40)mg/L,percentage of CD_(4)^(+) cell count<200 cells/μl was 60.00%,median CD_(4)^(+) cell count was 112.30(230.52)cells/μl,percentage of(1,3)-β-D glucan>200 pg/ml and lactate dehydrogenase>250 U/L were both 62.50%(10 cases),and the mean value of albumin was(27.08±4.04)g/L.Cytomegalovirus and/or EBV were detected by metagenomic next-generation sequencing in 9 of 16 patients(56.25%).Eigth of 13 cases were positive for cytomegalovirus DNA and/or EBV DNA in plasma.On the basis of treatment with compounded sulfamethoxazole in combination or not with echinocandins,75.00%(12/16)of patients used antiviral drugs,93.75%(15/16)used hormones,56.25%(9/16)used gammaglobulin,62.50%(10/16)used thymidine,and 93.75%(15/16)used other antimicrobials empirically or on target.Nine(56.25%)patients improved after treatment.CONCLUSIONS Patients with non-HIV Pneumocystis jirovecii pneumonia had more autoimmune underlying disease,predominately mixed infections,with higher morbidity and mortality,metagenomic next-generation sequencing technology could provide better pathogenetic evidence for this type of infection.In addition to compounded sulfamethoxazole and echinocandins for anti-Pneumocystis jirovecii therapy,the use of hormones,gammaglobulins,thymosin,and other antimicrobials should be individualized and require more clinical data.
作者
展冠军
孟珊珊
徐家兵
何杰
蒙钟经
李妮妮
刘中秋
陆瑾
ZHAN Guan-jun;MENG Shan-shan;XU Jia-bing;HE Jie;MENG Zhong-jing;LI Ni-ni;LIU Zhong-qiu;LU Jin(Zhongda Hospital Affiliated to Southeast University,Nanjing,Jiangsu 210009,China)
出处
《中华医院感染学杂志》
CAS
CSCD
北大核心
2024年第20期3046-3052,共7页
Chinese Journal of Nosocomiology
基金
江苏省自然科学基金资助项目(BK20200367)
南京药学会常州四药基金资助项目(2021YX020)。
关键词
耶氏肺孢子菌
重症肺炎
宏基因组二代测序
临床特征
用药分析
非人类免疫缺陷病毒
Pneumocystis jirovecii
Severe pneumonia
Metagenomic next-generation sequencing
Clinical features
Medication analysis
Non-human immunodeficiency virus
作者简介
展冠军(1970-),女,硕士,副主任药师,研究方向:临床药学及药事管理;通讯作者:陆瑾,E-mail:subwoofer365@sina.com。