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117株结核分枝杆菌临床分离株对注射用抗结核药物耐药水平的研究

Study on the levels of injectable antituberculosis drug resistance in 117 Mycobacterium tuberculosis clinical strains

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【作者】 宋艳华马丽萍陆宇付育红高孟秋

【Author】 SONG Yan-hua;MA Li-ping;LU Yu;FU Yu-hong;GAO Meng-qiu;Department of Tuberculosis,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumour Research Institute;

【机构】 首都医科大学附属北京胸科医院北京市结核病胸部肿瘤研究所结核科首都医科大学附属北京胸科医院药物研究室首都医科大学附属北京胸科医院国家结核病临床实验室

【摘要】 目的 对临床Mtb菌株进行链霉素(Sm)、卡那霉素(Km)、阿米卡星(Am)、卷曲霉素(Cm)的药物敏感性试验(简称“药敏试验”),了解其耐药程度和交叉耐药水平。方法 采用微孔板Alamar blue试验(microplate Alamar Blue assay,MABA),检测117株Mtb临床分离菌株的Sm、Km、Am和Cm的体外最低抑菌浓度(MIC)值。Sm、Km、Am、Cm的临界浓度分别为2、4、1、2.5/μg/ml。将Sm、Km、Am的MIC值大于临界浓度≤16μg/ml、32~64μg/ml、>64μg/ml分别为低度耐药、中度耐药、高度耐药;Cm的MIC值大于临界浓度≤20μg/ml、40~80μg/ml、>80μg/ml分别为低度耐药、中度耐药、高度耐药。结果 117株临床分离株中,83株耐Sm,其中63株(75.9%)为高度耐药,18株(21.7%)为低度耐药,2株(2.4%)中度耐药;23株耐Km和19株耐Am的耐药株中分别有78.3%(18/23)和94.7%(18/19)高度耐药,其余分别为两药的低度耐药菌株,未发现中度耐Km或Am的菌株;14株Cm耐药株的MIC值都在5~20μg/ml,未发现高度耐药株。83株Sm耐药的菌株中有27.7%(23/83)和22.9%(19/83)分别对Km和Am耐药,71.1%(59/83)对Am和Km均敏感。Km耐药株和Am耐药株中分别有78.3%(18/23)和94.7%(18/19)同时耐Km和Am(x~2=1.157,P>0.05),且对Km和Am均高度耐药;5株对Km低度耐药,但对Am敏感。Am耐药株和Cm耐药株中,分别有68.4%(13/19)和92.9%(13/14)同时耐Am和Cm。结论 耐Sm或Km或Am的Mtb临床分离株绝大多数为高度耐药,耐Cm的Mtb临床分离株以低度耐药为主;绝大多数的Sm高度耐药株仍对Am、Km敏感;高度耐Am或Km的菌株互为为完全交叉耐药,Km低度耐药的菌株对Am敏感;Am高度耐药株多数对Cm为低度耐药,绝大多数Cm耐药株对Am高度耐药。

【Abstract】 Objective To observe the levels of the resistance and cross-resistance to streptomycin(Sm),kanamycin(Km),amikacin(Am),capreomycin(Cm) in Mycobacterium tuberculosis(Mtb) clinical strains by drug susceptibility test(DST).Methods The MICs of Sm,Km,Am,and Cm in 117 Mtb clinical strains were detected by microplate Alamar blue assay(MABA).The critical concentration of Sm,Km,Am,and Cm on Mtb were 2,4,1 and 2.5 μg/ml,respectively.When the MICs of Sm/Km/Am on Mtb were greater than critical concentration and ≤16 μg/ml,or 32~64 μg/ml,or >64 jug/ml,the drug resistances were defined as low level,moderate level,and high level,respectively.But that for Cm on Mtb was greater than critical concentration and ≤20 μg/ml,or40-80 fig/ml,or >80 μg/ml.Results Of 117 Mtb clinical isolates,83 were Sm-resistant,in which 63 isolates(75.9%)were high resitance,18 isolates(21.7%) were low resistance,2 isolates(2.4%) were moderate resistance.78.3%of 23 Km-resistant strains and 94.7%of 19 Am-resistant strains were high-level resistance(MIC≥128 μg/ml),other isolates were low-level resistant to Am/Km,no moderate-level resistant isolates were observed.The MICs of 14 Cm-resistant isolates were 5-20 μg/ml,and there were not high level of Cm-resistant isolates.Of83 Sm-resistant isolates,27.7%(23/83) and 22.9%(19/83) were resistant to Km and Am respectively,71.1%(59/83) were sensitive to both Km and Am.78.3%(18/23) of Km-resistant isolates and 94.7%(18/19) of Amresistant isolates were highly resistant to both Km and Am,which had no significant difference(x~2= 1.157,P>0.05).Five strains were low resistance to Km,but sensitive to Am.68.4%(13/19) of Am-resistant isolates and92.9%(13/14) of Cm-resistant isolates were resistant to both Am and Cm.Conclusion The majority of the Sm/Km/Am-resistant clinical isolates were high resistance,and the majority of the Cm-resistant clinical isolates were low resistance.Most of highly Sm-resistant isolates were susceptible to Km/Am.The highly Am/Km-resistant isolates showed cross resistance each other.A small proportion of lowly Km-resistant isolates were sensitive to Am.Most of highly Am-resistant isolates were low resistance to Cm.Almost all of Cm-resistant isolates were high resistant to Am.

【基金】 北京市医院管理局临床医学发展专项(ZYLX201304)
  • 【文献出处】 中国防痨杂志 ,Chinese Journal of Antituberculosis , 编辑部邮箱 ,2015年04期
  • 【分类号】R446.5;R52
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