Article(id=1211269162958189093, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.04.05, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1605456000000, receivedDateStr=2020-11-16, revisedDate=1614268800000, revisedDateStr=2021-02-26, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718672742, onlineDateStr=2025-12-26, pubDate=1619539200000, pubDateStr=2021-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718672742, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718672742, creator=13701087609, updateTime=1766718672742, updator=13701087609, issue=Issue{id=1211269157790806494, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='4', pageStart='319', pageEnd='424', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718671510, creator=13701087609, updateTime=1766718756000, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269512217882745, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269512217882746, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=348, endPage=353, ext={EN=ArticleExt(id=1211269163348259379, articleId=1211269162958189093, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Co-infection of pulmonary aspergillosis and nocardiosis: A case report and literature review, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To summarize the clinical characteristics of patients suffering from invasive pulmonary aspergillosis(IPA) associated with pulmonary nocardiosis (PN) for improving the level in diagnosis and treatment of the disease. Methods The clinical characteristics, diagnosis and treatment of one patient diagnosed with IPA and PN in the First Medical Center of Chinese PLA General Hospital in January 2017 were reported. Wanfang, CNKI, PubMed, Web of Science and Embase databases were searched, and the clinical characteristics and diagnosis and treatment process of patients with IPA and PN were analyzed together with this patient. Results This patient was a 66-year-old male. His underlying disease was nephrotic syndrome, and long-term treatment with hormones and other immunosuppressive agents. The clinical manifestations were cough, yellow sputum, fever. Chest CT showed multiple nodules in both lungs. Aspergillus and Nocardia were found in the sputum. The patient was clearly diagnosed as "invasive pulmonary aspergillosis combined with pulmonary nocardiosis". After targeted anti-infective treatment, the patient recovered. Combined with the literature, a total of 24 cases of patient, including 16 males and 8 females, were analyzed; except for one patient who was infected after drowning, the other 23 patients had immunological impairment; all the patients received anti-infective treatment against Aspergillus and Nocardia, and a total of 6 deaths. Conclusions Patients with IPA may be associated with PN, and it is prone to occur in immunosuppressed patients. Attention should be paid to differential diagnosis during clinical diagnosis and treatment. Early diagnosis and treatment may have a positive effect on improving the prognosis.

, correspAuthors=Jun-Chang Cui, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 总结侵袭性肺曲霉病合并肺奴卡菌病的临床特点,提高对该疾病的诊治水平。方法 报告1例侵袭性肺曲霉病合并肺奴卡菌病例。检索万方数据库、中国期刊全文数据库、PubMed、Web of Science和Embase数据库,结合文献报告综合分析该类患者的临床特点及诊治过程。结果 本例患者为男性,66岁,基础疾病为肾病综合征,长期应用激素等免疫抑制剂治疗。临床表现为咳嗽、咳黄痰、发热;胸部CT显示双肺多发结节空洞影;痰中发现曲霉及奴卡菌。明确诊断为“侵袭性肺曲霉病合并肺奴卡菌病”,给予针对性抗感染治疗后痊愈。综合文献并本例患者,24例中男16例,女8例;除1例为溺水后感染外,其余23例均合并免疫功能受损。所有患者均接受针对曲霉和肺奴卡菌的抗感染治疗,6例死亡。结论 侵袭性肺曲霉病患者可能合并肺奴卡菌病,且易发生于免疫抑制的患者,临床诊治时须注意鉴别诊断。早期诊断和治疗可能对改善预后有积极意义。

, correspAuthors=崔俊昌, authorNote=null, correspAuthorsNote=
崔俊昌,E-mail:
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段智梅,医学硕士,主治医师,主要从事感染及呼吸危重症方面的研究

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段智梅,医学硕士,主治医师,主要从事感染及呼吸危重症方面的研究

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段智梅,医学硕士,主治医师,主要从事感染及呼吸危重症方面的研究

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Clin Microbiol Rev, 2006, 19(2): 259-282., articleTitle=Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy, refAbstract=null)], funds=[Fund(id=1211269170000425815, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, awardId=2016YFC1304301, language=EN, fundingSource=National Key Research and Development Program "Research on Prevention and Control of Major Chronic Noncommunicable Diseases" in 2016(2016YFC1304301), fundOrder=null, country=null), Fund(id=1211269170734429023, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, awardId=2016YFC1304301, language=CN, fundingSource=国家重点研发计划“重大慢性非传染性疾病防控研究”2016年度专项(2016YFC1304301), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1211269164849820262, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, xref=1, ext=[AuthorCompanyExt(id=1211269164866597481, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, companyId=1211269164849820262, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory and Critical Care Medicine, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China), AuthorCompanyExt(id=1211269164874986091, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, companyId=1211269164849820262, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1解放军总医院第一医学中心呼吸与危重症医学科,北京 100853)]), AuthorCompany(id=1211269164967260782, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, xref=2, ext=[AuthorCompanyExt(id=1211269164984038000, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, companyId=1211269164967260782, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Department of Critical Care Medicine, the 968th Hospital of PLA Joint Logistics Support Force, Jinzhou, Liaoning 121000, China), AuthorCompanyExt(id=1211269164988232305, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, companyId=1211269164967260782, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2解放军联勤保障部队第968医院重症医学科,辽宁 锦州 121000)])], figs=[ArticleFig(id=1211269168742134553, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=EN, label=Fig. 1, caption=Change trend of infection index, figureFileSmall=lwh80STyE3oxxSd4YDTRMg==, figureFileBig=KcISXxS/WOEIa9bLJJ8n+A==, tableContent=null), ArticleFig(id=1211269169056707359, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=CN, label=图1, caption=感染指标变化趋势, figureFileSmall=lwh80STyE3oxxSd4YDTRMg==, figureFileBig=KcISXxS/WOEIa9bLJJ8n+A==, tableContent=null), ArticleFig(id=1211269169325142830, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=EN, label=Fig.2, caption=Specific treatment plan of co-infection of pulmonary aspergillosis and nocardiosis, figureFileSmall=2kAOvCbaREzPU5O7r99zdQ==, figureFileBig=K+SJiEYrxvsadifYLMrm0A==, tableContent=null), ArticleFig(id=1211269169442583351, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=CN, label=图2, caption=侵袭性肺曲霉病合并肺奴卡菌病具体治疗方案, figureFileSmall=2kAOvCbaREzPU5O7r99zdQ==, figureFileBig=K+SJiEYrxvsadifYLMrm0A==, tableContent=null), ArticleFig(id=1211269169539052348, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=EN, label=Fig.3, caption=Chest CT of co-infection of pulmonary aspergillosis and nocardiosis, figureFileSmall=NNZSTPH2VIJIWIcJnQfnEw==, figureFileBig=dq4O4ZNr4ISYoM2mktjukQ==, tableContent=null), ArticleFig(id=1211269169648104259, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=CN, label=图3, caption=侵袭性肺曲霉病合并肺奴卡菌病患者复查胸部CT, figureFileSmall=NNZSTPH2VIJIWIcJnQfnEw==, figureFileBig=dq4O4ZNr4ISYoM2mktjukQ==, tableContent=null), ArticleFig(id=1211269169736184648, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=EN, label=Tab.1, caption=

Summary of clinical data of 24 patients co-infected with Aspergillus and Nocardia

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病例性别年龄(岁)基础疾病免疫抑制剂影像学治疗方案预后文献
166肾病综合征、膜性肾病激素、环磷酰胺结节+空洞伏立康唑+左氧氟沙星+米诺环素好转本病例
215慢性肉芽肿性疾病实变两性霉素B+氟胞嘧啶+TMP-SMX+红霉素好转[6]
361冠心病、心脏移植术后硫唑嘌呤、泼尼松、环孢素结节两性霉素B+TMP-SMX+异烟肼+更昔洛韦好转[7]
449肾移植术后硫唑嘌呤、泼尼松实变+空洞两性霉素B+TMP-SMX+红霉素+甲硝唑+异烟肼死亡[8]
534系膜毛细血管性肾炎、肾衰、透析、高血压环磷酰胺片、泼尼松实变+空洞伊曲康唑+亚胺培南西司他丁钠+TMP-SMX好转[9]
663缺血性心肌病,心脏移植术后泼尼松、硫唑嘌呤、环孢素实变两性霉素B+TMP-SMX+克拉霉素好转[10]
722溺水实变+空洞两性霉素B脂质体+美罗培南+TMP-SMX+阿米卡星好转[11]
850急性髓系白血病、造血干细胞移植后甲氨蝶呤、他克莫司、泼尼松、吗替麦考酚酯厚壁空洞、多发小空洞泊沙康唑+TMP-SMX好转[12]
967支气管扩张、淋巴瘤阿仑单抗等多种免疫抑制剂结节+实变+空洞两性霉素B脂质体+美罗培南+阿米卡星+TMP-SMX好转[13]
1065IPF右单肺移植他克莫司、硫唑嘌呤、泼尼松、马抗胸腺细胞球蛋白结节伏立康唑+亚胺培南西司他丁钠+阿米卡星+TMP-SMX好转[14]
11702型糖尿病、哮喘激素空洞伴液平伊曲康唑+TMP-SMX好转[15]
1237成人Still病激素、他克莫司实变+空洞+结节两性霉素B+伏立康唑+TMP-SMX好转[16]
1362COPD激素实变+空洞伏立康唑+亚胺培南西司他丁钠+TMP-SMX死亡[17]
1457哮喘泼尼松实变+空洞伏立康唑+美罗培南+TMP-SMX+阿米卡星好转[5]
1546鼻咽癌放化疗后、肉芽肿性血管炎激素实变+空洞伏立康唑+亚胺培南西司他丁钠+阿米卡星+TMP-SMX好转[5]
1651RA、双侧股骨头坏死激素实变+空洞伏立康唑+左氧氟沙星+TMP-SMX死亡[5]
1735重症哮喘激素实变伏立康唑+TMP-SMX好转[18]
1892高血压、糖尿病、血脂异常、巨细胞性动脉炎激素实变+空洞伏立康唑+亚胺培南西司他丁钠+利奈唑胺+TMP-SMX死亡[19]
1955ABPA、陈旧性肺结核激素实变+空洞伊曲康唑+TMP-SMX+美罗培南好转[20]
2064慢性淋巴细胞性白血病伊布替尼淋巴结肿大伏立康唑+万古霉素+哌拉西林钠他唑巴坦+TMP-SMX死亡[21]
2153霍奇金淋巴瘤化疗实变NA死亡[22]
2281B细胞非霍奇金淋巴瘤复发+糖尿病化疗实变+胸腔积液伏立康唑+美罗培南左氧+奥司他韦好转[23]
2339NA激素实变NA好转[24]
2453类固醇依赖性溃疡性结肠炎+COPD+霍奇金淋巴瘤Golimumab支扩NA好转[25]
), ArticleFig(id=1211269169866208078, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162958189093, language=CN, label=表1, caption=

24例IPA合并PN患者的临床资料

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病例性别年龄(岁)基础疾病免疫抑制剂影像学治疗方案预后文献
166肾病综合征、膜性肾病激素、环磷酰胺结节+空洞伏立康唑+左氧氟沙星+米诺环素好转本病例
215慢性肉芽肿性疾病实变两性霉素B+氟胞嘧啶+TMP-SMX+红霉素好转[6]
361冠心病、心脏移植术后硫唑嘌呤、泼尼松、环孢素结节两性霉素B+TMP-SMX+异烟肼+更昔洛韦好转[7]
449肾移植术后硫唑嘌呤、泼尼松实变+空洞两性霉素B+TMP-SMX+红霉素+甲硝唑+异烟肼死亡[8]
534系膜毛细血管性肾炎、肾衰、透析、高血压环磷酰胺片、泼尼松实变+空洞伊曲康唑+亚胺培南西司他丁钠+TMP-SMX好转[9]
663缺血性心肌病,心脏移植术后泼尼松、硫唑嘌呤、环孢素实变两性霉素B+TMP-SMX+克拉霉素好转[10]
722溺水实变+空洞两性霉素B脂质体+美罗培南+TMP-SMX+阿米卡星好转[11]
850急性髓系白血病、造血干细胞移植后甲氨蝶呤、他克莫司、泼尼松、吗替麦考酚酯厚壁空洞、多发小空洞泊沙康唑+TMP-SMX好转[12]
967支气管扩张、淋巴瘤阿仑单抗等多种免疫抑制剂结节+实变+空洞两性霉素B脂质体+美罗培南+阿米卡星+TMP-SMX好转[13]
1065IPF右单肺移植他克莫司、硫唑嘌呤、泼尼松、马抗胸腺细胞球蛋白结节伏立康唑+亚胺培南西司他丁钠+阿米卡星+TMP-SMX好转[14]
11702型糖尿病、哮喘激素空洞伴液平伊曲康唑+TMP-SMX好转[15]
1237成人Still病激素、他克莫司实变+空洞+结节两性霉素B+伏立康唑+TMP-SMX好转[16]
1362COPD激素实变+空洞伏立康唑+亚胺培南西司他丁钠+TMP-SMX死亡[17]
1457哮喘泼尼松实变+空洞伏立康唑+美罗培南+TMP-SMX+阿米卡星好转[5]
1546鼻咽癌放化疗后、肉芽肿性血管炎激素实变+空洞伏立康唑+亚胺培南西司他丁钠+阿米卡星+TMP-SMX好转[5]
1651RA、双侧股骨头坏死激素实变+空洞伏立康唑+左氧氟沙星+TMP-SMX死亡[5]
1735重症哮喘激素实变伏立康唑+TMP-SMX好转[18]
1892高血压、糖尿病、血脂异常、巨细胞性动脉炎激素实变+空洞伏立康唑+亚胺培南西司他丁钠+利奈唑胺+TMP-SMX死亡[19]
1955ABPA、陈旧性肺结核激素实变+空洞伊曲康唑+TMP-SMX+美罗培南好转[20]
2064慢性淋巴细胞性白血病伊布替尼淋巴结肿大伏立康唑+万古霉素+哌拉西林钠他唑巴坦+TMP-SMX死亡[21]
2153霍奇金淋巴瘤化疗实变NA死亡[22]
2281B细胞非霍奇金淋巴瘤复发+糖尿病化疗实变+胸腔积液伏立康唑+美罗培南左氧+奥司他韦好转[23]
2339NA激素实变NA好转[24]
2453类固醇依赖性溃疡性结肠炎+COPD+霍奇金淋巴瘤Golimumab支扩NA好转[25]
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侵袭性肺曲霉病合并肺奴卡菌病1例并文献复习
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段智梅 1 , 毛丹 2 , 徐轶 1 , 曹江涛 1 , 崔俊昌 1, *
解放军医学杂志 | 临床研究 2021,46(4): 348-353
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解放军医学杂志 | 临床研究 2021, 46(4): 348-353
侵袭性肺曲霉病合并肺奴卡菌病1例并文献复习
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段智梅1, 毛丹2, 徐轶1, 曹江涛1, 崔俊昌1, *
作者信息
  • 1解放军总医院第一医学中心呼吸与危重症医学科,北京 100853
  • 2解放军联勤保障部队第968医院重症医学科,辽宁 锦州 121000
  • 段智梅,医学硕士,主治医师,主要从事感染及呼吸危重症方面的研究

通讯作者:

崔俊昌,E-mail:
Co-infection of pulmonary aspergillosis and nocardiosis: A case report and literature review
Zhi-Mei Duan1, Dan Mao2, Yi Xu1, Jiang-Tao Cao1, Jun-Chang Cui1, *
Affiliations
  • 1Department of Respiratory and Critical Care Medicine, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • 2Department of Critical Care Medicine, the 968th Hospital of PLA Joint Logistics Support Force, Jinzhou, Liaoning 121000, China
出版时间: 2021-04-28 doi: 10.11855/j.issn.0577-7402.2021.04.05
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目的 总结侵袭性肺曲霉病合并肺奴卡菌病的临床特点,提高对该疾病的诊治水平。方法 报告1例侵袭性肺曲霉病合并肺奴卡菌病例。检索万方数据库、中国期刊全文数据库、PubMed、Web of Science和Embase数据库,结合文献报告综合分析该类患者的临床特点及诊治过程。结果 本例患者为男性,66岁,基础疾病为肾病综合征,长期应用激素等免疫抑制剂治疗。临床表现为咳嗽、咳黄痰、发热;胸部CT显示双肺多发结节空洞影;痰中发现曲霉及奴卡菌。明确诊断为“侵袭性肺曲霉病合并肺奴卡菌病”,给予针对性抗感染治疗后痊愈。综合文献并本例患者,24例中男16例,女8例;除1例为溺水后感染外,其余23例均合并免疫功能受损。所有患者均接受针对曲霉和肺奴卡菌的抗感染治疗,6例死亡。结论 侵袭性肺曲霉病患者可能合并肺奴卡菌病,且易发生于免疫抑制的患者,临床诊治时须注意鉴别诊断。早期诊断和治疗可能对改善预后有积极意义。

侵袭性肺曲霉病  /  肺奴卡菌病  /  免疫抑制

Objective To summarize the clinical characteristics of patients suffering from invasive pulmonary aspergillosis(IPA) associated with pulmonary nocardiosis (PN) for improving the level in diagnosis and treatment of the disease. Methods The clinical characteristics, diagnosis and treatment of one patient diagnosed with IPA and PN in the First Medical Center of Chinese PLA General Hospital in January 2017 were reported. Wanfang, CNKI, PubMed, Web of Science and Embase databases were searched, and the clinical characteristics and diagnosis and treatment process of patients with IPA and PN were analyzed together with this patient. Results This patient was a 66-year-old male. His underlying disease was nephrotic syndrome, and long-term treatment with hormones and other immunosuppressive agents. The clinical manifestations were cough, yellow sputum, fever. Chest CT showed multiple nodules in both lungs. Aspergillus and Nocardia were found in the sputum. The patient was clearly diagnosed as "invasive pulmonary aspergillosis combined with pulmonary nocardiosis". After targeted anti-infective treatment, the patient recovered. Combined with the literature, a total of 24 cases of patient, including 16 males and 8 females, were analyzed; except for one patient who was infected after drowning, the other 23 patients had immunological impairment; all the patients received anti-infective treatment against Aspergillus and Nocardia, and a total of 6 deaths. Conclusions Patients with IPA may be associated with PN, and it is prone to occur in immunosuppressed patients. Attention should be paid to differential diagnosis during clinical diagnosis and treatment. Early diagnosis and treatment may have a positive effect on improving the prognosis.

invasive pulmonary aspergillosis  /  pulmonary nocardiosis  /  immunosuppression
段智梅, 毛丹, 徐轶, 曹江涛, 崔俊昌. 侵袭性肺曲霉病合并肺奴卡菌病1例并文献复习. 解放军医学杂志, 2021 , 46 (4) : 348 -353 . DOI: 10.11855/j.issn.0577-7402.2021.04.05
Zhi-Mei Duan, Dan Mao, Yi Xu, Jiang-Tao Cao, Jun-Chang Cui. Co-infection of pulmonary aspergillosis and nocardiosis: A case report and literature review[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (4) : 348 -353 . DOI: 10.11855/j.issn.0577-7402.2021.04.05
免疫抑制患者易发生机会性感染[1]。侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)及肺奴卡菌病(pulmonary nocardiosis,PN)均为肺部机会感染性疾病。IPA以烟曲霉菌为主要感染菌,主要发病人群为免疫缺陷患者,该病临床表现无特异性,诊断困难,预后差,病死率极高[2]。PN是由奴卡菌引起的少见且严重的化脓性或肉芽肿性疾病,常见发病人群为免疫功能低下的患者,通常被误诊为其他细菌感染、结核、真菌感染、恶性肿瘤等,有较高的病死率[3]。IPA及PN的危险因素包括长期使用糖皮质激素或免疫抑制剂、艾滋病、实体器官移植和造血干细胞移植受者、糖尿病等,二者均可局限于肺部,也可以播散到肺部以外的器官,如中枢神经系统、皮肤软组织等[2-3]。曲霉和奴卡菌虽均为肺部机会性感染菌,但曲霉及奴卡菌混合感染临床比较少见。在临床工作中,我们发现这两种感染可同时存在于同一患者,引起更复杂的临床情况。现报道我院1例IPA合并PN患者的临床特点,并结合相关文献进行复习,以期提高对此类患者的认识。
患者男,66岁,2016年5月诊断为肾病综合征,给予泼尼松、雷公藤多苷片、环磷酰胺等治疗6个月,控制良好。2016年11月15日无明显诱因出现高热,体温最高达40℃,伴咳嗽、咳黄色痰、畏寒,无胸痛、咯血等症状,给予美罗培南抗感染治疗,症状稍缓解。2016年11月25日胸部CT提示右肺上叶斑片状密度增高影,内可见空洞形成,左肺上叶多发条索影,双肺下叶间质改变。血真菌D-葡聚糖(G试验)207.5 pg/ml,半乳甘露聚糖(Gm试验)0.48 μg/L;痰真菌培养发现曲霉2次。结合以下表现临床诊断为侵袭性肺曲霉病:患者长期应用免疫抑制剂;临床表现咳嗽、咳痰、发热等症状,抗细菌治疗效果不佳;影像学表现为右肺新发密度增高影伴空洞形成;痰培养2次发现曲霉。2016年11月29日给予伏立康唑抗真菌治疗,咳嗽、咳痰好转,体温降至正常,痰培养曲霉阴性。复查胸部CT右肺上叶病灶较前有所吸收。应用伏立康唑治疗55 d后,于2017年1月20日再次出现发热,体温最高39.6℃,畏寒,偶有咳嗽,咳少量痰。2017年1月24日复查胸部CT提示右肺上叶结节空洞影较前明显吸收,但双肺新发多发斑片状密度增高影及结节影,部分病灶内可见空洞形成。因“咳嗽、咳痰、间断发热2月余”于2017年1月25日收入解放军总医院第一医学中心呼吸与危重症医学科。
血常规白细胞计数4.1×109/L、中性粒细胞0.759;C反应蛋白测定16.1 mg/dl、白细胞介素–6 138.0 pg/ml、降钙素原0.147 ng/ml,感染指标变化趋势如图1所示。G试验47.5 pg/ml、Gm试验0.33 μg/L,均为阴性。痰涂片抗酸杆菌、结核菌群鉴定及耐药基因检测、结核3项、TB-SPOT试验均为阴性。
入科后给予伏立康唑(0.2 g/次,1次/12 h)、左氧氟沙星(0.5 g/次,1次/d)、利奈唑胺片(0.6 g/次,1次/12 h)、美罗培南(1.0 g/次,1次/8 h)联合抗感染治疗。4 d后患者一般情况好转,体温降至正常。痰培养结果示奴卡菌属生长,诊断为IPA合并PN。头颅核磁检查未见异常。2017年2月4日复查胸部CT提示:右肺上叶结节空洞影较前吸收,双肺新发斑片状密度增高影及结节影,病灶内可见空洞且较2017年1月24日增多、增大,考虑患者肺部阴影吸收滞后,诊断仍考虑为IPA合并PN。继续伏立康唑、左氧氟沙星、利奈唑胺片、美罗培南抗感染治疗。2017年2月17日复查胸部CT双肺阴影明显吸收,于2月21日出院,院外继续口服左氧氟沙星片、米诺环素、伏立康唑治疗半年,具体治疗方案如图2所示。2017年6月28日复查胸部CT双肺病灶基本吸收(图3)。
以“曲霉”“奴卡菌”组合为关键词,在万方数据库和中国期刊全文数据库中进行检索,截至2020年9月30日,共检索到1篇中文文献[4]。以“aspergillosis”“nocardiosis”为关键词,在PubMed、Web of Science及Embase数据库检索到20篇外文文献[5-24]并获取全文。文献报道23例患者,结合本研究1例,共24例(表1)。其中男性16例,女性8例,年龄15~92岁。除1例为溺水后感染外,其余患者均有基础免疫功能受损,基础疾病包括支气管哮喘、慢性阻塞性肺疾病、糖尿病、结缔组织病、恶性肿瘤放化疗后、实体器官移植术后、血液系统恶性肿瘤、造血干细胞移植术后等。混合感染患者的临床症状主要有发热、咳嗽、咳痰,随病情进展,可出现喘憋、呼吸衰竭、感染性休克、多器官衰竭等表现[4-5,12,16,18],但也有患者无发热及呼吸系统症状[6,15]。影像学表现主要为斑片状实变、结节,其内伴单发或多发、大小不等空洞影,无显著的区域特征,薄壁空洞与厚壁空洞共存。支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)为主要的病原学来源(13/24),其他还包括CT或超声引导下肺穿刺活检、开胸肺活检、电视胸腔镜辅助下楔形肺切除术后标本。其中1例患者痰、支气管吸物、BALF和尸检肺组织病理均找到奴卡菌及曲霉[16],另1例生前BALF中找到曲霉菌,后经尸检病理找到曲霉及奴卡菌[7]。24例均接受了针对曲霉和奴卡菌的抗感染治疗,最长疗程为12个月。24例中,重症肺炎12例,多表现为高热、白细胞及中性粒细胞明显升高;最终死亡6例;其余18例患者经过针对两种病原的联合治疗后,临床症状很快得到缓解,但胸部影像学改善较慢。本院患者经4个多月的联合治疗后,病灶基本吸收(图3)。
曲霉是一种广泛存在于自然界的条件致病菌,经呼吸道吸入大量的曲霉孢子可引起肺部真菌感染性疾病,烟曲霉为最常见的感染菌属,典型临床表现为发热、胸痛及咯血等。其高危因素有血液系统恶性肿瘤、器官移植术后、中性粒细胞减少、长期使用抗生素或激素、糖尿病及结构性肺病等[2]。影像学表现为斑片状实变影、结节影,结节影内可见单发或多发空洞影、新月征或晕轮征等。由于烟曲霉对唑类抗生素的耐药性正在增加,因此,在免疫缺陷的重症IPA患者中,推荐将唑类抗生素与棘白菌素类联合使用[25]
奴卡菌为革兰染色阳性分枝棒状需氧菌,属放线菌目,具有弱抗酸性,广泛存在于土壤、空气、粉尘、淡水、海水和腐败的植物中[26]。奴卡菌可经消化道、呼吸道、皮肤伤口侵入人体,引起局限性或播散性化脓性疾病,肺是主要受累器官。PN多发生于T细胞免疫缺陷人群,如艾滋病(acquired immunodeficiency syndrome,AIDS)或人类免疫缺陷病毒感染(human immunodeficiency virus,HIV)、恶性血液病、造血干细胞移植后、实体器官移植后、结缔组织病、肿瘤放疗和化疗后、长期应用激素和(或)免疫抑制剂等以及慢性肉芽肿性疾病、糖尿病等[3,25]。该病亦常见于患有慢性基础性肺疾病的患者,如哮喘、慢性阻塞性肺疾病、支气管扩张、结节病、肺泡蛋白沉积症等,考虑与该类患者长期、大剂量激素治疗有关[27]。咳嗽是最常见的临床症状,其他临床症状还包括发热、咳脓痰、咯血、胸痛、胸闷气促、体重减轻、疲乏、盗汗等[27]。实验室检查可出现白细胞、中性粒细胞及C反应蛋白升高。影像学有多种表现,主要为单个或多个大小不一的结节/肿块影、肺叶或肺段的实变影、空洞、胸腔积液等。肺奴卡菌感染的诊断需要从临床标本(痰或肺泡灌洗液)中分离鉴定出该微生物。奴卡菌生长缓慢,需氧培养下需2~7 d,有时甚至需4~6周,因此如临床怀疑奴卡菌感染应告知检验人员,以提高阳性率[28],同时进行痰涂片弱抗酸染色检查也可以提高检出率。PN的一线治疗药物是甲氧苄氨嘧啶-磺胺甲噁唑(trimethoprim-sulfamethoxazole,TMP-SMX),本例患者由于对磺胺类药物过敏,故未选用TMP-SMX。目前研究表明磺胺药物耐药率增高,建议给予以TMP-SMX为基础的联合治疗[3],联合应用的药物可选择阿米卡星、头孢曲松、碳青霉烯类、利奈唑胺、米诺环素、莫西沙星、左氧氟沙星等[26-27]。文献中23例患者大部分采用了以TMP-SMX为基础的联合治疗,联合应用的药物有阿米卡星、碳青霉烯类、利奈唑胺以及呼吸喹诺酮类等。对于免疫缺陷或中枢神经系统感染的患者疗程为12个月[25]
由上可见,曲霉和奴卡菌感染在危险因素、临床表现及影像学特征等方面均有相似之处,因此临床上二者须相互鉴别,同时还要考虑混合感染的可能性。免疫抑制患者出现重症肺部感染,临床医师常凭借自身经验选用呼吸喹诺酮类、三代头孢类抗生素联合酶抑制剂或者碳青霉烯类抗生素作为起始治疗方案,这些方案有很大的概率覆盖奴卡菌感染,使得初始治疗方案有效,但由于治疗疗程不足,易造成病情反复。临床医师对曲霉相对熟悉,其培养周期短,易于识别,因此在明确某种病原并进行针对性治疗后,若病情无明显好转或出现反复,要考虑混合感染可能,并再次进行病原学检查。如本病例在给予针对曲霉的治疗后病情出现反复,胸部影像学进展,进一步行病原学检查诊断为侵袭性肺曲霉病合并肺奴卡菌病。
本研究共涉及24例患者,其中6例死亡。混合感染是严重影响使用免疫抑制剂患者长期生存的重要危险因素,早期诊断及治疗可能对改善预后有积极意义。本研究的不足之处在于病例数较少,有待扩大样本量,对IPA合并PN患者的临床特点进行更深入的探讨。
  • 国家重点研发计划“重大慢性非传染性疾病防控研究”2016年度专项(2016YFC1304301)
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doi: 10.11855/j.issn.0577-7402.2021.04.05
  • 接收时间:2020-11-16
  • 首发时间:2025-12-26
  • 出版时间:2021-04-28
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  • 收稿日期:2020-11-16
  • 修回日期:2021-02-26
基金
National Key Research and Development Program "Research on Prevention and Control of Major Chronic Noncommunicable Diseases" in 2016(2016YFC1304301)
国家重点研发计划“重大慢性非传染性疾病防控研究”2016年度专项(2016YFC1304301)
作者信息
    1解放军总医院第一医学中心呼吸与危重症医学科,北京 100853
    2解放军联勤保障部队第968医院重症医学科,辽宁 锦州 121000

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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