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Article(id=1200024245695770649, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200024241572770746, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1756.2023.0328, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1660838400000, receivedDateStr=2022-08-19, revisedDate=null, revisedDateStr=null, acceptedDate=1665763200000, acceptedDateStr=2022-10-15, onlineDate=1764037675546, onlineDateStr=2025-11-25, pubDate=1695830400000, pubDateStr=2023-09-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764037675546, onlineIssueDateStr=2025-11-25, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764037675546, creator=13701087609, updateTime=1764037675546, updator=13701087609, issue=Issue{id=1200024241572770746, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='9', pageStart='993', pageEnd='1112', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764037674563, creator=13701087609, updateTime=1764038723302, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1200028640353288193, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200024241572770746, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1200028640353288194, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200024241572770746, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1055, endPage=1060, ext={EN=ArticleExt(id=1200024245997760554, articleId=1200024245695770649, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of drug resistance in 118 cases with bone and joint tuberculosis, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the drug resistance features of 118 patients with bone and joint tuberculosis. Methods The clinical data of 118 joint tuberculosis patients who were hospitalized in Beijing Chest Hospital from January 2016 to January 2022 were retrospectively analyzed. Drug susceptibility test was performed for the following 16 drugs streptomycin (Sm), isoniazid (INH), rifampicin (RFP), ethambutol (EMB), rifapentine (Rft), levofloxacin (Lfx), amikacin (Am), capreomycin (Cm), prothionamide (Pto), isoniazid aminosalicylate (Pa), moxifloxacin (Mfx), p-aminosalicylic acid (PAS), clarithromycin (Clr), rifabutin (Rfb), kanamycin (Km) and clofazimine (Cfz). Analyze the Mycobacterium tuberculosis culture results, drug sensitivity results, initial or retreatment status of patients with bone and joint tuberculosis, as well as the drug resistance types of patients diagnosed with bone and joint tuberculosis by etiology. Results The total drug resistance rate of 118 bone and joint tuberculosis patients to at least one of the 16 drugs was 28.0%(33/118), of which the drug resistance rate was significantly higher in previously treated patients than in new patients with statistically significant difference [70.0%(21/30) vs. 13.6%(12/88), P<0.001]. The top seven drug resistance rate of bone and joint tuberculosis to the 16 drugs were: Sm, INH, RFP, Rft, Rfb, Pa and Clr, and the top seven drug resistance rates of new patients were: Sm, INH, Clr, Pa, RFP, Rft and PAS, and the top seven drug resistance rates of in previously treated patients were: Sm, RFP, Rft, Rfb, INH, Pa and EMB. The mono-resistance rate of bone and joint tuberculosis, poly-drug resistance rate of spinal tuberculosis, and multidrug-resistance rate were 7.6%(9/118), 8.5%(10/118), and 11.9%(14/118), respectively. There was no significant difference of the mono-resistance rate of bone and joint tuberculosis between new patients and in previously treated patients [6.8%(6/88) vs. 10.0%(3/30), P=0.691], but the poly-drug resistance rate and the multidrug-resistance rate were significantly higher in previously treated patients than in new patients, and the differences were statistically significant [20.0%(6/30) vs. 4.5%(4/88), P=0.017; 40.0%(12/30) vs. 2.3%(2/88), P<0.001]. Conclusions There was serious epidemic of drug resistance in bone and joint tuberculosis. While performing surgical treatment, clinicians should develop effective drug treatment regimens according to the results of drug sensitivity tests.

, correspAuthors=Gui-Rong Wang, authorNote=null, correspAuthorsNote=
E-mail:
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目的 分析118例骨关节结核住院患者的耐药特点。方法 回顾性分析2016年1月-2022年6月首都医科大学附属北京胸科医院收治的118例骨关节结核住院患者的临床资料。采用药敏试验检测来自118例患者的结核分枝杆菌对链霉素(Sm)、异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、利福喷丁(Rft)、左氧左旋氧氟沙星(Lfx)、阿米卡星(Am)、卷曲霉素(Cm)、丙硫异烟胺(Pto)、对氨基水杨酸异烟肼(Pa)、莫西沙星(Mfx)、对氨基水杨酸(PAS)、克拉霉素(Clr)、利福布汀(Rfb)、卡那霉素(Km)和氯法齐明(Cfz)的敏感性，分析骨关节结核患者的结核分枝杆菌培养结果、药敏试验结果、初治或复治情况，以及病原学确诊为骨关节结核初治与复治患者耐药类型的差异。结果 118例骨关节结核患者对16种抗结核药的总耐药率为28.0%(33/118)，复治患者的总耐药率明显高于初治患者，差异有统计学意义[70.0%(21/30) vs. 13.6%(12/88)，P<0.001]。118例骨关节结核患者任一耐药率顺位前7位为Sm、INH、RFP、Rft、Rfb、Pa和Clr，初治患者任一耐药率顺位前7位为Sm、INH、Clr、Pa、RFP、Rft和PAS，复治患者任一耐药率顺位前7位为Sm、RFP、Rft、Rfb、INH、Pa和EMB。118例骨关节结核患者的总单耐药率、总多耐药率、总耐多药率依次为7.6%(9/118)、8.5%(10/118)、11.9%(14/118)。初治患者与复治患者的单耐药率差异无统计学意义[6.8%(6/88) vs. 10.0%(3/30)，P=0.691]，复治患者多耐药率和耐多药率明显高于初治患者[20.0%(6/30) vs. 4.5%(4/88)，P=0.017；40.0%(12/30) vs. 2.3%(2/88)，P<0.001]。结论 骨关节结核耐药问题严重，临床医师在行手术治疗的同时，应根据药敏试验结果制定有效的药物治疗方案。

, correspAuthors=王桂荣, authorNote=null, correspAuthorsNote=
王桂荣，E-mail：
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王潮虹，硕士研究生，主要从事结核病实验室诊断方面的研究

, authorsList=王潮虹, 孙晴, 廖鑫磊, 晏君, 龙嗣博, 郑迈克, 赵艳, 王桂荣)}, authors=[Author(id=1200024248065552506, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1200024248157827199, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, authorId=1200024248065552506, language=EN, stringName=Chao-Hong Wang, firstName=Chao-Hong, middleName=null, lastName=Wang, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1200024248283656325, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, authorId=1200024248065552506, language=CN, stringName=王潮虹, firstName=潮虹, middleName=null, lastName=王, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=首都医科大学附属北京胸科医院检验科，北京 101149, bio={"content":"

王潮虹，硕士研究生，主要从事结核病实验室诊断方面的研究

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王潮虹，硕士研究生，主要从事结核病实验室诊断方面的研究

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Characteristics and management of bone and joint tuberculosis in native and migrant population in Shanghai during 2011 to 2015[J]. BMC Infect Dis, 2018, 18(1): 543., articleTitle=Characteristics and management of bone and joint tuberculosis in native and migrant population in Shanghai during 2011 to 2015, refAbstract=null), Reference(id=1200024262540095958, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, doi=null, pmid=null, pmcid=null, year=2022, volume=44, issue=9, pageStart=940, pageEnd=946, url=null, language=null, rfNumber=[21], rfOrder=28, authorNames=Wang CH, Sun Q, Liao XL, journalName=Chin J Antitubercul, refType=null, unstructuredReference=Wang CH, Sun Q, Liao XL, et al. Analysis of drug resistance situation of Mycobacterium tuberculosis strains from 231 spinal tuberculosis patients[J]. Chin J Antitubercul, 2022, 44(9): 940-946., articleTitle=Analysis of drug resistance situation of Mycobacterium tuberculosis strains from 231 spinal tuberculosis patients, refAbstract=null), Reference(id=1200024265530634713, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, doi=null, pmid=null, pmcid=null, year=2022, volume=44, issue=9, pageStart=940, pageEnd=946, url=null, language=null, rfNumber=[21], rfOrder=29, authorNames=王潮虹, 孙晴, 廖鑫磊, journalName=中国防痨杂志, refType=null, unstructuredReference=王潮虹, 孙晴, 廖鑫磊, 等. 231例脊柱结核患者耐药情况分析[J]. 中国防痨杂志, 2022, 44(9): 940-946., articleTitle=231例脊柱结核患者耐药情况分析, refAbstract=null)], funds=[Fund(id=1200024257553068404, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=2022-3-040, language=EN, fundingSource=Beijing Public Health Experts Project(2022-3-040), fundOrder=null, country=null), Fund(id=1200024257741812088, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=2022-3-040, language=CN, fundingSource=北京市高层次公共卫生技术人才项目(2022-3-040), fundOrder=null, country=null), Fund(id=1200024257905389948, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=KJ2022CX044, language=EN, fundingSource=Beijing Tongzhou Municipal Science and Technology Commission(KJ2022CX044), fundOrder=null, country=null), Fund(id=1200024257997664640, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=KJ2022CX044, language=CN, fundingSource=北京市通州区科技计划项目(KJ2022CX044), fundOrder=null, country=null), Fund(id=1200024258123493764, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=YH201917, language=EN, fundingSource=Beijing Tongzhou District High Level Talent Development Support Plan(YH201917), fundOrder=null, country=null), Fund(id=1200024258295460235, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, awardId=YH201917, language=CN, fundingSource=北京市通州区“两高”人才工程(YH201917), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1200024247956500589, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, xref=null, ext=[AuthorCompanyExt(id=1200024247964889199, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, companyId=1200024247956500589, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China), AuthorCompanyExt(id=1200024247977472113, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, companyId=1200024247956500589, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=首都医科大学附属北京胸科医院检验科，北京 101149)])], figs=[ArticleFig(id=1200024254839353658, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Fig.1, caption=Distribution of patients with bone and joint tuberculosis in different age groups, figureFileSmall=/HzfcvsxGrtlxP3Um59c+A==, figureFileBig=lmPhec06Cd6Gf7waA78Amg==, tableContent=null), ArticleFig(id=1200024254960988480, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=图1, caption=不同年龄段骨关节结核患者分布情况, figureFileSmall=/HzfcvsxGrtlxP3Um59c+A==, figureFileBig=lmPhec06Cd6Gf7waA78Amg==, tableContent=null), ArticleFig(id=1200024255166509386, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Tab.1, caption=

Sociological and clinical characteristics of 118 patients with bone and joint tuberculosis [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

性别
男67(56.8)47(53.4)20(66.7)
女51(43.2)41(46.6)10(33.3)
年龄(岁)
0~104(3.4)4(4.5)0
10~2010(8.5)8(9.1)2(6.7)
20~3017(14.4)8(9.1)9(30.0)
30~4020(16.9)12(13.6)8(26.7)
40~5011(9.3)9(10.2)2(6.7)
50~6026(22.0)20(22.7)6(20.0)
60~7018(15.3)16(18.2)2(6.7)
70~8011(9.3)10(11.4)1(3.3)
>801(0.8)1(1.1)0
职业
农民58(49.2)41(46.6)17(56.7)
工人2(1.7)1(1.1)1(3.3)
退(离)休人员18(15.3)16(18.2)2(6.7)
无业人员9(7.6)4(4.5)5(16.7)
学生12(10.2)8(9.1)4(13.3)
职员4(3.4)3(3.4)1(3.3)
其他a15(12.7)10(11.4)5(16.7)
并发肺结核23(19.5)9(10.2)14(46.7)
基础疾病
营养不良47(39.8)35(39.8)12(40.0)
高血压22(18.6)19(21.6)3(10.0)
冠心病8(6.8)5(5.7)3(10.0)
糖尿病8(6.8)6(6.8)2(6.7)
免疫性疾病2(1.7)2(2.3)0
), ArticleFig(id=1200024255296532813, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=表1, caption=

118例骨关节结核患者的社会学和临床特征[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

性别
男67(56.8)47(53.4)20(66.7)
女51(43.2)41(46.6)10(33.3)
年龄(岁)
0~104(3.4)4(4.5)0
10~2010(8.5)8(9.1)2(6.7)
20~3017(14.4)8(9.1)9(30.0)
30~4020(16.9)12(13.6)8(26.7)
40~5011(9.3)9(10.2)2(6.7)
50~6026(22.0)20(22.7)6(20.0)
60~7018(15.3)16(18.2)2(6.7)
70~8011(9.3)10(11.4)1(3.3)
>801(0.8)1(1.1)0
职业
农民58(49.2)41(46.6)17(56.7)
工人2(1.7)1(1.1)1(3.3)
退(离)休人员18(15.3)16(18.2)2(6.7)
无业人员9(7.6)4(4.5)5(16.7)
学生12(10.2)8(9.1)4(13.3)
职员4(3.4)3(3.4)1(3.3)
其他a15(12.7)10(11.4)5(16.7)
并发肺结核23(19.5)9(10.2)14(46.7)
基础疾病
营养不良47(39.8)35(39.8)12(40.0)
高血压22(18.6)19(21.6)3(10.0)
冠心病8(6.8)5(5.7)3(10.0)
糖尿病8(6.8)6(6.8)2(6.7)
免疫性疾病2(1.7)2(2.3)0
), ArticleFig(id=1200024255393001807, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Tab.2, caption=

Distribution of disease sites in 118 patients with bone and joint tuberculosis [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
患病部位

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

关节结核
膝关节32(27.1)20(22.7)12(40.0)
髋关节14(11.9)7(8.0)7(23.3)
肩关节10(8.5)5(5.7)5(16.7)
肘关节8(6.8)8(9.1)0
踝关节9(7.6)8(9.1)1(3.3)
腕关节5(4.2)4(4.5)1(3.3)
骶髂关节4(3.4)3(3.4)1(3.3)
胸锁关节5(4.2)3(3.4)2(6.7)
骨结核
胸骨1(0.8)01(3.3)
股骨6(5.1)5(5.7)1(3.3)
骶骨1(0.8)1(1.1)0
胫骨1(0.8)1(1.1)0
跟骨2(1.7)2(2.3)0
腭骨1(0.8)1(1.1)0
尺骨1(0.8)1(1.1)0
髂骨1(0.8)01(3.3)
耻骨2(1.7)2(2.3)0
肋骨1(0.8)1(1.1)0
骰骨1(0.8)1(1.1)0
涉及两个及以上部位10(8.5)7(8.0)3(10.0)
合并脊柱结核10(8.5)8(9.1)2(6.7)
), ArticleFig(id=1200024256584184152, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=表2, caption=

118例骨关节结核患者患病部位分布情况[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
患病部位

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

关节结核
膝关节32(27.1)20(22.7)12(40.0)
髋关节14(11.9)7(8.0)7(23.3)
肩关节10(8.5)5(5.7)5(16.7)
肘关节8(6.8)8(9.1)0
踝关节9(7.6)8(9.1)1(3.3)
腕关节5(4.2)4(4.5)1(3.3)
骶髂关节4(3.4)3(3.4)1(3.3)
胸锁关节5(4.2)3(3.4)2(6.7)
骨结核
胸骨1(0.8)01(3.3)
股骨6(5.1)5(5.7)1(3.3)
骶骨1(0.8)1(1.1)0
胫骨1(0.8)1(1.1)0
跟骨2(1.7)2(2.3)0
腭骨1(0.8)1(1.1)0
尺骨1(0.8)1(1.1)0
髂骨1(0.8)01(3.3)
耻骨2(1.7)2(2.3)0
肋骨1(0.8)1(1.1)0
骰骨1(0.8)1(1.1)0
涉及两个及以上部位10(8.5)7(8.0)3(10.0)
合并脊柱结核10(8.5)8(9.1)2(6.7)
), ArticleFig(id=1200024256831648088, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Tab.3, caption=

Distribution of drug resistance types among 118 newly treated and retreated patients with bone and joint tuberculosis [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

χ2P
任一耐药33(28.0)12(13.6)21(70.0)35.282<0.001
Sm27(22.9)8(9.1)19(63.3)37.304<0.001
INH18(15.3)4(4.5)14(46.7)37.705<0.001
RFP18(15.3)2(2.3)16(53.3)45.122<0.001
Rft18(15.3)2(2.3)16(53.3)-<0.001a
Rfb17(14.4)1(1.1)16(53.3)-<0.001a
Pa15(12.7)4(4.5)11(36.7)-<0.001a
Clr6(5.1)4(4.5)2(6.7)-0.643a
PAS4(3.4)2(2.3)2(6.7)-0.267a
EMB3(2.5)03(10.0)-0.015a
Pto2(1.7)02(6.7)-0.063a
Cfz2(1.7)1(1.1)1(3.3)-0.445a
Lfx1(0.8)01(3.3)-0.254a
Cm1(0.8)1(1.1)0-1.000a
Am000--
Km000--
Mfx000--
), ArticleFig(id=1200024256965865823, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=表3, caption=

任一耐药类型在118例初治和复治骨关节结核患者中的分布情况[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

合计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

χ2P
任一耐药33(28.0)12(13.6)21(70.0)35.282<0.001
Sm27(22.9)8(9.1)19(63.3)37.304<0.001
INH18(15.3)4(4.5)14(46.7)37.705<0.001
RFP18(15.3)2(2.3)16(53.3)45.122<0.001
Rft18(15.3)2(2.3)16(53.3)-<0.001a
Rfb17(14.4)1(1.1)16(53.3)-<0.001a
Pa15(12.7)4(4.5)11(36.7)-<0.001a
Clr6(5.1)4(4.5)2(6.7)-0.643a
PAS4(3.4)2(2.3)2(6.7)-0.267a
EMB3(2.5)03(10.0)-0.015a
Pto2(1.7)02(6.7)-0.063a
Cfz2(1.7)1(1.1)1(3.3)-0.445a
Lfx1(0.8)01(3.3)-0.254a
Cm1(0.8)1(1.1)0-1.000a
Am000--
Km000--
Mfx000--
), ArticleFig(id=1200024257091694948, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Tab.4, caption=

Distribution of different poly-drug resistance types in 118 newly treated and retreated patients with bone and joint tuberculosis [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

总计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

Pa
合计10(8.5)4(4.5)6(20.0)0.017
Sm+INH1(0.8)01(3.3)0.254
Sm+INH+Clr1(0.8)01(3.3)0.254
Sm+INH+Pa1(0.8)1(1.1)01.000
INH+Cm+Pa1(0.8)1(1.1)01.000
PAS+Clr+Cfz1(0.8)1(1.1)01.000
RFP+Rft+Rfb1(0.8)01(3.3)0.254
Sm+Pa+PAS+Clr1(0.8)1(1.1)01.000
Sm+RFP+Rft+Rfb1(0.8)01(3.3)0.254
Sm+RFP+EMB+Rft+Pa+Rfb1(0.8)01(3.3)0.254
Sm+RFP+Rft+Lfx+Pa+PAS+Rfb1(0.8)01(3.3)0.254
), ArticleFig(id=1200024257221718373, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=表4, caption=

不同多耐药类型在118例骨关节结核初治复治患者中的分布情况[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

总计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

Pa
合计10(8.5)4(4.5)6(20.0)0.017
Sm+INH1(0.8)01(3.3)0.254
Sm+INH+Clr1(0.8)01(3.3)0.254
Sm+INH+Pa1(0.8)1(1.1)01.000
INH+Cm+Pa1(0.8)1(1.1)01.000
PAS+Clr+Cfz1(0.8)1(1.1)01.000
RFP+Rft+Rfb1(0.8)01(3.3)0.254
Sm+Pa+PAS+Clr1(0.8)1(1.1)01.000
Sm+RFP+Rft+Rfb1(0.8)01(3.3)0.254
Sm+RFP+EMB+Rft+Pa+Rfb1(0.8)01(3.3)0.254
Sm+RFP+Rft+Lfx+Pa+PAS+Rfb1(0.8)01(3.3)0.254
), ArticleFig(id=1200024257309798763, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=EN, label=Tab.5, caption=

Distribution of different types of multidrug resistance in 118 newly treated and retreated patients with bone and joint tuberculosis [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

总计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

Pa
INH+RFP14(11.9)2(2.3)12(40.0)<0.001
INH+RFP+Rft+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Rfb2(1.7)1(1.1)1(3.3)0.445
INH+RFP+Sm+Rft+Pa1(0.8)1(1.1)01.000
INH+RFP+Sm+Rft+Pa+Rfb4(3.4)04(13.3)0.004
INH+RFP+Sm+Rft+Pa+Clr1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Pto+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+EMB+Rft+Pa+Rfb2(1.7)02(6.7)0.063
INH+RFP+Sm+Rft+Pto+Pa+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Pa+PAS+Rfb+Cfz1(0.8)01(3.3)0.254
), ArticleFig(id=1200024257410462060, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1200024245695770649, language=CN, label=表5, caption=

不同耐多药类型在118例骨关节结核初治复治患者中的分布情况[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
耐药类型

总计
(n=118)

初治患者
(n=88)

复治患者
(n=30)

Pa
INH+RFP14(11.9)2(2.3)12(40.0)<0.001
INH+RFP+Rft+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Rfb2(1.7)1(1.1)1(3.3)0.445
INH+RFP+Sm+Rft+Pa1(0.8)1(1.1)01.000
INH+RFP+Sm+Rft+Pa+Rfb4(3.4)04(13.3)0.004
INH+RFP+Sm+Rft+Pa+Clr1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Pto+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+EMB+Rft+Pa+Rfb2(1.7)02(6.7)0.063
INH+RFP+Sm+Rft+Pto+Pa+Rfb1(0.8)01(3.3)0.254
INH+RFP+Sm+Rft+Pa+PAS+Rfb+Cfz1(0.8)01(3.3)0.254
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118例骨关节结核耐药情况分析
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王潮虹 , 孙晴 , 廖鑫磊 , 晏君 , 龙嗣博 , 郑迈克 , 赵艳 , 王桂荣 *
解放军医学杂志 | 临床研究 2023,48(9): 1055-1060
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解放军医学杂志 | 临床研究 2023, 48(9): 1055-1060
118例骨关节结核耐药情况分析
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王潮虹, 孙晴, 廖鑫磊, 晏君, 龙嗣博, 郑迈克, 赵艳, 王桂荣*
作者信息
  • 首都医科大学附属北京胸科医院检验科，北京 101149

    • 王潮虹，硕士研究生，主要从事结核病实验室诊断方面的研究

通讯作者:

王桂荣，E-mail：
Analysis of drug resistance in 118 cases with bone and joint tuberculosis
Chao-Hong Wang, Qing Sun, Xin-Lei Liao, Jun Yan, Si-Bo Long, Mai-Ke Zheng, Yan Zhao, Gui-Rong Wang*
Affiliations
  • Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
出版时间: 2023-09-28 doi: 10.11855/j.issn.0577-7402.1756.2023.0328
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摘要
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目的 分析118例骨关节结核住院患者的耐药特点。方法 回顾性分析2016年1月-2022年6月首都医科大学附属北京胸科医院收治的118例骨关节结核住院患者的临床资料。采用药敏试验检测来自118例患者的结核分枝杆菌对链霉素(Sm)、异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、利福喷丁(Rft)、左氧左旋氧氟沙星(Lfx)、阿米卡星(Am)、卷曲霉素(Cm)、丙硫异烟胺(Pto)、对氨基水杨酸异烟肼(Pa)、莫西沙星(Mfx)、对氨基水杨酸(PAS)、克拉霉素(Clr)、利福布汀(Rfb)、卡那霉素(Km)和氯法齐明(Cfz)的敏感性，分析骨关节结核患者的结核分枝杆菌培养结果、药敏试验结果、初治或复治情况，以及病原学确诊为骨关节结核初治与复治患者耐药类型的差异。结果 118例骨关节结核患者对16种抗结核药的总耐药率为28.0%(33/118)，复治患者的总耐药率明显高于初治患者，差异有统计学意义[70.0%(21/30) vs. 13.6%(12/88)，P<0.001]。118例骨关节结核患者任一耐药率顺位前7位为Sm、INH、RFP、Rft、Rfb、Pa和Clr，初治患者任一耐药率顺位前7位为Sm、INH、Clr、Pa、RFP、Rft和PAS，复治患者任一耐药率顺位前7位为Sm、RFP、Rft、Rfb、INH、Pa和EMB。118例骨关节结核患者的总单耐药率、总多耐药率、总耐多药率依次为7.6%(9/118)、8.5%(10/118)、11.9%(14/118)。初治患者与复治患者的单耐药率差异无统计学意义[6.8%(6/88) vs. 10.0%(3/30)，P=0.691]，复治患者多耐药率和耐多药率明显高于初治患者[20.0%(6/30) vs. 4.5%(4/88)，P=0.017；40.0%(12/30) vs. 2.3%(2/88)，P<0.001]。结论 骨关节结核耐药问题严重，临床医师在行手术治疗的同时，应根据药敏试验结果制定有效的药物治疗方案。

结核，骨关节  /  药物敏感性试验  /  耐药性，耐多药

Objective To analyze the drug resistance features of 118 patients with bone and joint tuberculosis. Methods The clinical data of 118 joint tuberculosis patients who were hospitalized in Beijing Chest Hospital from January 2016 to January 2022 were retrospectively analyzed. Drug susceptibility test was performed for the following 16 drugs streptomycin (Sm), isoniazid (INH), rifampicin (RFP), ethambutol (EMB), rifapentine (Rft), levofloxacin (Lfx), amikacin (Am), capreomycin (Cm), prothionamide (Pto), isoniazid aminosalicylate (Pa), moxifloxacin (Mfx), p-aminosalicylic acid (PAS), clarithromycin (Clr), rifabutin (Rfb), kanamycin (Km) and clofazimine (Cfz). Analyze the Mycobacterium tuberculosis culture results, drug sensitivity results, initial or retreatment status of patients with bone and joint tuberculosis, as well as the drug resistance types of patients diagnosed with bone and joint tuberculosis by etiology. Results The total drug resistance rate of 118 bone and joint tuberculosis patients to at least one of the 16 drugs was 28.0%(33/118), of which the drug resistance rate was significantly higher in previously treated patients than in new patients with statistically significant difference [70.0%(21/30) vs. 13.6%(12/88), P<0.001]. The top seven drug resistance rate of bone and joint tuberculosis to the 16 drugs were: Sm, INH, RFP, Rft, Rfb, Pa and Clr, and the top seven drug resistance rates of new patients were: Sm, INH, Clr, Pa, RFP, Rft and PAS, and the top seven drug resistance rates of in previously treated patients were: Sm, RFP, Rft, Rfb, INH, Pa and EMB. The mono-resistance rate of bone and joint tuberculosis, poly-drug resistance rate of spinal tuberculosis, and multidrug-resistance rate were 7.6%(9/118), 8.5%(10/118), and 11.9%(14/118), respectively. There was no significant difference of the mono-resistance rate of bone and joint tuberculosis between new patients and in previously treated patients [6.8%(6/88) vs. 10.0%(3/30), P=0.691], but the poly-drug resistance rate and the multidrug-resistance rate were significantly higher in previously treated patients than in new patients, and the differences were statistically significant [20.0%(6/30) vs. 4.5%(4/88), P=0.017; 40.0%(12/30) vs. 2.3%(2/88), P<0.001]. Conclusions There was serious epidemic of drug resistance in bone and joint tuberculosis. While performing surgical treatment, clinicians should develop effective drug treatment regimens according to the results of drug sensitivity tests.

tuberculosis, bone and joint  /  antimicrobial susceptibility test  /  drug resistance  /  multidrug resistance
王潮虹, 孙晴, 廖鑫磊, 晏君, 龙嗣博, 郑迈克, 赵艳, 王桂荣. 118例骨关节结核耐药情况分析. 解放军医学杂志, 2023 , 48 (9) : 1055 -1060 . DOI: 10.11855/j.issn.0577-7402.1756.2023.0328
Chao-Hong Wang, Qing Sun, Xin-Lei Liao, Jun Yan, Si-Bo Long, Mai-Ke Zheng, Yan Zhao, Gui-Rong Wang. Analysis of drug resistance in 118 cases with bone and joint tuberculosis[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (9) : 1055 -1060 . DOI: 10.11855/j.issn.0577-7402.1756.2023.0328
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骨关节结核是一种常见的肺外结核，占所有结核病的3%~10%，占肺外结核的15%[1]。近年来，骨关节结核发病率呈上升趋势[2-3]。耐药结核病作为严重的公共卫生问题，越来越受到社会的关注[4]。临床上抗结核治疗的不规范，新型抗结核药的研究进展缓慢，以及病灶中耐药菌株的存在和播散，致使骨关节结核治疗效果不佳且防控难度增大，给患者带来了巨大的经济负担和心理压力[5]。鉴于骨关节结核严峻的耐药形势，本研究分析了118例骨关节结核患者的临床特征及病原菌耐药性，以期为临床医师制定合理的个体化用药方案提供参考。
1 资料与方法
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1.1 研究对象
通过首都医科大学附属北京胸科医院电子病历管理系统回顾性收集2016年1月-2022年6月收治的118例骨关节结核住院患者的临床资料。纳入标准：脓液或组织标本经分枝杆菌培养和菌种鉴定为结核分枝杆菌；分离到的结核分枝杆菌进行了16种抗结核药物敏感性试验。本研究通过本院伦理委员会审查(LW-2022-010)。
1.2 方法
1.2.1 资料收集
收集患者的性别、年龄、病史、药物敏感性试验结果等相关资料。
1.2.2 分枝杆菌培养
按照《结核病诊断实验室检查规程》推荐的方法，采用改良罗氏或MGIT960培养法培养脓液或组织标本。
1.2.3 菌种鉴定
对于在含对硝基苯甲酸培养基上不生长、初步鉴定为结核分枝杆菌复合群的菌株，参照文献[6-8]的方法联合测定16S rRNA、rpoB、16S~23S rRNA间隔区(internally transcribed spacer，ITS)和hsp65基因序列，基因测序结果在http://www.ncbi.nlm.nih.gov网站上进行Blast比对，确定菌种类型。
1.2.4 药物敏感性试验
应用分枝杆菌微孔板药敏检测试剂盒(培养法；珠海银科医学工程股份有限公司)测定结核分枝杆菌对链霉素(streptomycin，Sm)、异烟肼(isoniazid，INH)、利福平(rifampicin，RFP)、乙胺丁醇(ethambutol，EMB)、利福喷丁(rifapentine，Rft)、左氧左旋氧氟沙星(levofloxacin，Lfx)、阿米卡星(amikacin，Am)、卷曲霉素(capreomycin，Cm)、丙硫异烟胺(prothionamide，Pto)、对氨基水杨酸异烟肼(pasiniazid，Pa)、莫西沙星(moxifloxacin，Mfx)、对氨基水杨酸(p-aminosalicylic acid，PAS)、克拉霉素(clarithromycin，Clr)、利福布汀(rifabutin，Rfb)、卡那霉素(kanamycin，Km)和氯法齐明(clofazimine，Cfz)的敏感性。
1.3 相关定义
参照《耐药结核病化学治疗指南(2015)》[9]，单耐药指结核分枝杆菌经体外药敏试验证实对一种抗结核药耐药；多耐药指结核分枝杆菌经体外药敏试验证实对一种以上一线抗结核药耐药但不包括同时对RFP和INH耐药；耐多药指结核分枝杆菌经体外药敏试验证实至少同时对RFP和INH耐药；交叉耐药是结核分枝杆菌经体外药敏试验证实对一种抗结核药耐药后，同时对另一种结构近似或作用性质相同的抗结核药耐药。
初治患者是指从未因结核病应用过抗结核药治疗，或使用抗结核药治疗<1个月；复治患者是指既往不规律使用抗结核药治疗≥1个月以及初治失败和复发者[10]。
1.4 观察指标
分析骨关节结核患者的结核分枝杆菌培养结果、药敏试验结果、初治或复治情况，以及病原学确诊为骨关节结核初治与复治患者的耐药类型。
1.5 统计学处理
应用SPSS 24.0软件进行统计分析。计数资料以率(%)表示，初治、复治患者耐药率的比较采用χ2检验或Fisher精确概率检验。P<0.05为差异有统计学意义。
2 结果
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2.1 一般资料
共纳入结核分枝杆菌培养阳性骨关节结核患者118例，其中初治患者88例(74.6%)，复治患者30例(25.4%)；男67例(56.8%)，女51例(43.2%)，男女比例为1.31∶1。年龄1~84岁，中位年龄48岁，发病年龄呈M形双波峰形态(图1)，20~40岁和50~70岁年龄段患者较多。农民患者58例，占49.2%(表1)。
118例骨关节结核患者中，膝关节感染者占比最高，为27.1%(32/118)，其次为髋关节感染者[11.9%(14/118)]；其中涉及两个及以上骨关节部位感染者占8.5%(10/118)，合并脊柱结核感染者占8.5%(10/118) (表2)。
2.2 骨关节结核患者总体耐药情况
2.2.1 总耐药率
118例骨关节结核患者分离菌株的总耐药率为28.0%(33/118)，复治患者的总耐药率明显高于初治患者，差异有统计学意义[70.0%(21/30) vs. 13.6%(12/88)，χ²=35.282，P<0.001，表3]。
2.2.2 任一耐药率
118例骨关节结核患者分离菌株对16种抗结核药任一耐药率顺位前7位为Sm、INH、RFP、Rft、Rfb、Pa和Clr；初治患者任一耐药率顺位前7位为Sm、INH、Clr、Pa、RFP、Rft和PAS；复治患者任一耐药率顺位前7位为Sm、RFP、Rft、Rfb、INH、Pa和EMB(表3)。
2.3 骨关节结核患者耐药类型分布
2.3.1 单耐药情况
118例骨关节结核患者分离菌株中，仅对一种结核药耐药9株，总单耐药率为7.6%(9/118)。初治患者与复治患者单耐药率比较差异无统计学意义[6.8%(6/88) vs. 10.0%(3/30)，P=0.691]。
2.3.2 多耐药情况
118例骨关节结核患者分离菌株中，多耐药菌株10株，总多耐药率为8.5%(10/118)。复治患者的多耐药率高于初治患者，差异有统计学意义[20.0%(6/30) vs. 4.5%(4/88)，P=0.017，表4]。
2.3.3 耐多药情况
118例骨关节结核患者分离菌株中，同时对INH和RFP耐药的菌株共14株，总耐多药率为11.9%(14/118)。复治患者的耐多药率明显高于初治患者，差异有统计学意义[40.0%(12/30) vs. 2.3%(2/88)，P<0.001，表5]。
2.3.4 交叉耐药情况
RFP与Rfb、Rft的交叉耐药率分别为94.4%(17/18)、100.0%(18/18)；Rfb与RFP、Rft的交叉耐药率分别为100.0%(17/17)、100.0%(17/17)；Rft与RFP、Rfb的交叉耐药率分别为100.0%(18/18)、94.4%(17/18)。
2.4 复治骨关节结核患者初治时抗结核治疗方案及耐药情况
30例复治骨关节结核患者中，初治时27例为敏感患者，3例为耐药患者。27例敏感患者中，81.5%(22/27)初治采用了规范的HREZ抗结核或手术治疗方案，18.5%(5/27)初治采用了HREZ联用氟喹诺酮类抗结核药物治疗。初治采用规范抗结核治疗的骨关节结核复治患者中，10例(45.5%，10/22)对一线抗结核药任一耐药；采用规范抗结核药联用氟喹诺酮类药物的5例复治患者均对一线抗结核药任一耐药，无患者对氟喹诺酮类药物产生耐药。
3 讨论
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肺外结核是指发生于肺部以外脏器的结核病，是结核病的重要组成部分[11-12]，其中骨结核居所有肺外结核的第3位，次于胸膜和淋巴结结核[2]。骨关节结核约占骨科结核总数的30%，主要累及膝关节、髋关节、肩关节、踝关节等较大的承重关节[2,13-14]，结核病病原菌通过淋巴系统和血液循环系统进入骨骼和关节，进行侵蚀破坏，侵蚀残留物可能造成骨关节的进一步坍塌和变形，增加不良结局的发生风险[12]，故骨关节结核患者病残率高，治疗难度大，给患者家庭和社会带来了沉重负担。因此，骨关节结核已成为临床医师和结核病研究人员研究的重点，其有效的治疗手段为手术固定与药物治疗相结合[15]。
2021年WHO全球结核病年报显示，2020年我国新增结核病患者84.2万例，仅次于印度，居于全球第2位[16]。2020年中国新诊断病原学阳性结核病患者中，共检出耐多药结核病(multi-drug resistant tuberculosis，MDR-TB)/利福平耐药结核病(rifampicin resistance-tuberculosis，RR-TB) 16 343例，准广泛耐药或广泛耐药结核病1185例，合计17 528例。由此可见，我国是结核病高负担国家，结核病耐药形势不容乐观。对于结核病尤其是MDR-TB的控制，是疾病防治及我国公共卫生工作最首要、最棘手的问题之一[17]。本研究结果显示，来自于骨关节结核患者的118株结核分枝杆菌的总耐药率为28.0%(33/118)，总多耐药率为8.5%(10/118)，总耐多药率为11.9%(14/118)，与第五次全国结核病流行病学调查[18]结果相比，总耐多药率高于全国调查数据(11.9% vs. 6.8%)。复治患者的多耐药率和耐多药率明显高于初治患者(20.0% vs. 4.5%，P=0.017；40.0% vs. 2.3%，P<0.001)，表明复治骨关节结核患者的耐药情况较为严重。
骨关节结核发病常不典型，诊断具有一定难度，临床上可通过手术获取标本进行细菌学检查。本研究118例骨关节结核患者中，16.9%(20/118)未进行手术治疗，这部分患者通过穿刺活检或收集伤口分泌物等方式进行细菌学诊断。因此，对于初治患者，临床医师应根据药敏结果制定合理的治疗方案，保证连续治疗，同时患者应遵医嘱规律服药、合理营养饮食以提高自身免疫力，降低疾病复发的可能性；对于复治患者，临床医师应采取更谨慎的措施，因为这类患者的耐药率明显高于全国平均水平，根据分离菌株的药敏试验结果，在常规一线抗结核药的基础上合理使用二线抗结核药，以提高治疗效果。
本研究118例骨关节结核患者的发病年龄呈M形双波峰形态，高发年龄段为20~40岁和50~70岁，分别占31.4%(37/118)和37.3%(44/118)，与其他研究结果一致[2,19]，分析原因可能为20~40岁年龄段人群处于事业起步期，学习工作压力大，而50~70岁年龄段人群发病率高可能与更年期有关。本研究中118例骨关节结核患者的职业主要为农民，占49.2%(58/118)，分析原因可能为农民从事农业耕种过程中易导致骨骼关节损伤，且接受健康教育的水平低或经济收入较低，增加了就诊和治疗的难度。本研究纳入的118例骨关节结核患者中，营养不良者占39.8%(47/118)，合并高血压、冠心病、糖尿病和免疫性疾病者分别占18.6%(22/118)、6.8%(8/118)、6.8%(8/118)和1.7%(2/118)。有研究显示，糖尿病、高血压等基础疾病可能影响患者的免疫系统，导致他们易暴露于结核病病原体而发病[20]。本组118例中，膝关节感染者占比最高[27.1%(32/118)]，其次为髋关节感染者[11.9%(14/118)]，涉及两个及以上骨关节部位感染者占8.5%(10/118)，合并脊柱结核感染者占8.8%(10/118)，表明承重量大的骨骼关节更易感染结核菌。
脊柱结核和骨关节结核同属于骨结核，前者约占骨结核总数的70%。笔者对2016年1月-2021年12月北京胸科医院收治的脊柱结核住院患者的临床特征及耐药情况进行分析，结果显示，脊柱结核患者对16种药物总耐药率为34.63%(80/231)，其中初治和复治患者的耐药率分别为21.26%(37/174)和75.44%(43/57)[21]。与本研究相比，两者总耐药率无统计学差异[34.63%(80/231) vs. 28.0%(33/118)，P=0.208]。由此可见，骨结核的耐药形势严峻，耐药发生率较高。
骨关节结核除采用手术治疗外，通常需要长时间的规范药物治疗，初治不彻底易导致疾病复发，引发耐药结核病的概率极高。临床上在治疗初发骨关节结核时，建议及时进行耐药性监测，掌握患者耐药状况，结合临床症状，采取规范措施，提高治疗成功率。
综上所述，骨关节结核诊断难度大且耐药形势严峻，临床上在对患者行手术治疗的同时，应根据药敏试验结果制定有效的药物治疗方案，进而提高治疗成功率。本研究存在一定局限性：研究对象仅来自北京胸科医院，不能完全代表骨关节结核人群；标本较难获取，且含菌量较低，可能影响药敏试验结果。未来仍需进一步开展多中心、大样本研究以全面、深入地分析骨关节结核的药物敏感性。
基金
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  • 北京市高层次公共卫生技术人才项目(2022-3-040)
  • 北京市通州区科技计划项目(KJ2022CX044)
  • 北京市通州区“两高”人才工程(YH201917)
文献
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2023年第48卷第9期
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doi: 10.11855/j.issn.0577-7402.1756.2023.0328
  • 接收时间：2022-08-19
  • 首发时间：2025-11-25
  • 出版时间：2023-09-28
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  • 收稿日期：2022-08-19
  • 录用日期：2022-10-15
基金
Beijing Public Health Experts Project(2022-3-040)
北京市高层次公共卫生技术人才项目(2022-3-040)
Beijing Tongzhou Municipal Science and Technology Commission(KJ2022CX044)
北京市通州区科技计划项目(KJ2022CX044)
Beijing Tongzhou District High Level Talent Development Support Plan(YH201917)
北京市通州区“两高”人才工程(YH201917)
作者信息
    首都医科大学附属北京胸科医院检验科，北京 101149

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王桂荣，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
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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