摘要
目的 研究莫西沙星耐药菌株的耐药相关基因突变特征,以及不同突变类型与莫西沙星最低抑菌浓度(minimum inhibitory concentration,MIC)的关系。方法 选取2019—2021年鄂尔多斯市第二人民医院检验科(162株)和首都医科大学附属北京胸科医院细菌免疫室(103株)保存的结核分枝杆菌,采用微孔板稀释法检测这些菌株对莫西沙星的MIC,同时对莫西沙星耐药菌株的DNA拓扑异构酶亚基A (gyrase subunit A,gyr A)和DNA拓扑异构酶亚基B (gyrase subunit B,gyr B)基因进行测序,统计莫西沙星耐药率的差异。结果 本研究总计纳入265株结核分枝杆菌,所有菌株中对莫西沙星耐药82株,耐药率为30.9%。耐多药结核分枝杆菌(multidrug resistant tuberculosis,MDR-TB)和非MDRTB菌株中,莫西沙星耐药率分别为46.1%(70/152)和10.6%(12/113),MDR-TB菌株耐药率显著高于非MDR-TB菌株(P<0.01)。在82株莫西沙星耐药菌株中,总计有59株(72.0%)和3株(3.7%)分别检测到携带gyr A基因突变或/和gyr B基因突变,最常见的突变在gyr A基因的94位点密码子(50.0%)。在gyr A和gyr B突变中,结核分枝杆菌的现代型(30.4%)和古代型(32.0%)差异无统计学意义;gyr A基因的90位点突变株、94位点天冬氨酸突变为酪氨酸以及丙氨酸菌株和gyr B基因突变株大部分表现为对莫西沙星低水平耐药(MIC<2μg/ml);而gyr A基因91位点突变株和94位点由天冬氨酸突变为甘氨酸以及丙氨酸引起高水平莫西沙星耐药,分别有75.0%、53.6%和46.2%的突变菌株(MIC≥2μg/ml)。结论 gyr A基因的94位点突变是莫西沙星耐药菌株最主要的耐药机制,不同gyr A和gyr B突变类型导致对莫西沙星不同的耐药水平。MDR-TB菌株中有46%的菌株对莫西沙星耐药,提示在使用氟喹诺酮前有必要开展药敏试验,以期制订合理的治疗方案。
Objective To investigate the mutation characteristics of drug-resistant genes among moxifloxacin-resistant Mycobacterium tuberculosis isolates,and the relationship between different mutant types and minimal inhibitory concentrations(MICs)against moxifloxacin.Methods The M.tuberculosis isolates were enrolled from clinical laboratory of The Second Peoples Hospital of Ordos(162 strains)and Department of Bacteriology and Immunology,Beijing Chest Hospital,Capital Medical University(103 strains)included during 2019-2021.Microporous plate dilution method was used to detect these strains of minimum bacteriostatic concentration(MIC)against moxifloxacin.At the same time,moxifloxacin-resistant isolates were sequenced for genetic mutations in gyrase subunit A(gyrA)and gyrB.The difference of drug resistance rate of moxifloxacin was statistically significant with P<0.05.Results A total of 265 Mycobacterium tuberculosis isolates were enrolled in this study,of which 82 were resistant to moxifloxacin,with a drug resistance rate of 30.9%.In multidrug-resistant tuberculosis(MDR-TB)and non-MDR-TB strains,the drug resistance rate of moxifloxacin was 46.1%(70/152)and 10.6%(12/113),respectively,and the drug resistance rate of MDR-TB strains was significantly higher than that of non-MDR-TB strains(P<0.01).Of the 82 isolates resistant to moxifloxacin,a total of 59(72.0%)and 3(3.7%)were detected to carry gyrA gene mutations or/and gyrB gene mutations,respectively,with the most common mutations at gyrA gene codon 94(50.0%).Among gyrA and gyrB mutations,there was no statistical difference between the modern(30.4%)and ancient types(32.0%)of Mycobacterium tuberculosis.gyrA gene mutant strain 90,aspartic acid mutant tyrosine at 94,alanine strain and gyrB gene mutant strain mostly showed low resistance to moxifloxacin(MIC<2μg/ml).However,high levels of moxifloxacin resistance were caused by mutation at gyrA gene 91 and aspartic acid mutation to glycine and alanine at gyrA gene 94,with 75.0%,53.6%and 46.2%of the mutant strains MIC≥2μg/ml,respectively.Conclusions Locus 94 mutation of gyrA gene is one of the main moxifloxacin-resistant strains of resistant mechanism,and different gyrA and gyrB mutations lead to different resistant level for moxifloxacin.46%of strains with MDR-TB were resistant to moxifloxacin,suggesting the need for drug sensitive test before the use of fluoroquinolone in order to formulate a reasonable treatment regimen.
作者
孙海林
任卫聪
尚媛媛
刘娟
Sun Hailin;Ren Weicong;Shang Yuanyuan;Liu Juan(Key Disciplines of Tuberculosis,The Second Peoples Hospital of Ordos,Ordos 017000,Inner Mongolia Autonomous Region,China;Department of Bacteriology and Immunology,Beijing Chest Hospital,Beijing Tuberculosis and Thoracic Tumor Research Institute,Capital Medical University,Beijing 101149,China)
出处
《中国医学前沿杂志(电子版)》
CSCD
2023年第10期67-72,共6页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
关键词
结核分枝杆菌
氟喹诺酮
莫西沙星
最低抑菌浓度
北京基因型
Mycobacterium tuberculosis
Fluoroquinolones
Moxifloxacin
Minimal inhibitory concentration
Beijing gen-otype