首页|经宏基因组二代测序技术确诊的非HIV耶氏肺孢子菌重症肺炎患者临床特征及药物治疗

经宏基因组二代测序技术确诊的非HIV耶氏肺孢子菌重症肺炎患者临床特征及药物治疗

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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)×109/L,C-反应蛋白为(111。51±81。40)mg/L,CD4+T 细胞计数<200 个/μl为 60。00%(9/15),CD4+T 细胞计数中位数为 112。30(230。52)个/μl,(1,3)-β-D葡聚糖>200 pg/ml及乳酸脱氢酶>250 U/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。
Clinical characteristics and medication analysis of patients with non-HIV Pneumocystis jirovecii severe pneumonia confirmed by metagenomic next-generation sequencing
OBJECTIVE To investigate clinical characteristics of patients with non-HIV Pneumocystis jirovecii(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 Af-filiated to Southeast University and diagnosed by metagenomic next-generation sequencing on bronchoalveolar lav-age fluid and/or blood in combination with clinically confirmed diagnosis from Jan.2021 to Dec.2023,and the un-derlying 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 kid-ney 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)X 109/L,mean C-reactive protein value was(111.51±81.40)mg/L,percentage of CD4+cell count<200 cells/μl was 60.00%,median CD4+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 al-bumin was(27.08±4.04)g/L.Cytomegalovirus and/or EBV were detected by metagenomic next-generation se-quencing 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 echino-candins,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 Pneumocys-tis 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-Pneumo-cystis jirovecii therapy,the use of hormones,gammaglobulins,thymosin,and other antimicrobials should be in-dividualized and require more clinical data.

Pneumocystis jiroveciiSevere pneumoniaMetagenomic next-generation sequencingClinical fea-turesMedication analysisNon-human immunodeficiency virus

展冠军、孟珊珊、徐家兵、何杰、蒙钟经、李妮妮、刘中秋、陆瑾

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东南大学附属中大医院药剂科,江苏南京 210009

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

江苏省自然科学基金资助项目南京药学会常州四药基金资助项目

BK202003672021YX020

2024

中华医院感染学杂志
中华预防医学会 中国人民解放军总医院

中华医院感染学杂志

CSTPCD北大核心
影响因子:1.885
ISSN:1005-4529
年,卷(期):2024.34(20)