2009—2013年全国抗结核药物敏感性试验熟练度测试分析

doi:10.3969/j.issn.1000-6621.2015.02.007

摘要/Abstract

摘要： 目的评价和分析2009—2013年全国抗结核药物敏感性试验（简称“药敏试验”）熟练度测试结果，改善我国结核病实验室药敏试验能力。方法 2009—2013年对全国有能力开展药敏试验的省级、地市级508个结核病实验室每年寄发30株Mtb菌株进行8种抗结核药物［异烟肼(H)、链霉素(S)、乙胺丁醇(E)、利福平(R)、卡那霉素(Km)、阿米卡星(Am)、卷曲霉素(Cm)、氧氟沙星(Ofx)］的药敏试验熟练度测试,药敏试验方法采用WHO推荐的基于罗氏培养基的比例法。共计收到508个实验室报告的一线抗结核药物药敏试验熟练度测试结果，445个实验室报告的二线抗结核药物药敏试验熟练度测试结果。结果统一由国家结核病参比实验室进行比对。评价指标为敏感度、特异度、重复性和一致性。2009—2013年各指标差异采用卡方检验，变化趋势采用Cochran-Armitage趋势检验，以P<0.05为差异有统计学意义。结果对于各个药物总敏感度、总特异度、总重复性和总一致性的范围是：H：91.88%～97.62%、92.01%～98.33%、86.55%～95.27%和91.40%～97.60%；S：88.79%～94.14%、87.59%～91.36%、77.37%～93.13%和88.20%～92.45%；E：66.24%～85.17%、83.22%～97.87%、63.46%～89.76%和75.78%～90.80%；R：78.54%～96.34%、96.19%～98.07%、79.11%～95.66%和90.72%～97.21%；Km:81.12%～95.46%、95.35%～98.86%、94.12%～96.84%和90.23%～97.77%；Am：93.14%～98.94%、96.16%～99.00%、93.52%～97.94%和95.59%～98.19%；Cm：52.45%～95.68%、89.68%～97.85%、89.48%～92.99%和89.08%～95.61%；Ofx：84.75%～94.38%、96.21%～98.90%、88.01%～94.41%和93.01%～96.90%。除S的总特异度、Km和Cm的总重复性每年差异无统计学意义外（χ²值分别为8.49、4.1和7.78，P值均>0.05），各个药物的总敏感度每年差异有统计学意义(H：χ²=134.76；S：χ²=44.12；E：χ²=266.22；R：χ²=256.35；Km：χ²=197.46；Am：χ²=12.16；Cm：χ²=433.50；Ofx：χ²=47.38，P值均<0.05)；其他各个药物的总特异度每年差异有统计学意义(H：χ²=67.69；E：χ²=439.39；R：χ²=16.61；Km：χ²=94.97；Am：χ²=52.96；Cm：χ²=139.51；Ofx：χ²=11.66，P值均<0.05)；其他各个药物的总重复性每年差异有统计学意义(H：χ²=61.82；S：χ²=127.15；E：χ²=246.49；R：χ²=180.03；Am：χ²=21.65；Ofx：χ²=28.49，P值均<0.05)；各个药物的总一致性每年差异有统计学意义(H：χ²=162.05；S：χ²=36.58；E：χ²=369.11；R：χ²=152.30；Km：χ²=233.69；Am：χ²=32.55；Cm：χ²=168.79；Ofx：χ²=36.97，P值均<0.05)。除Am、Cm的总敏感度，Ofx的总特异度，Km、Am、Cm的总重复性逐年趋势检验无统计学意义外（Z值分别为0.46、0.99、－0.30、－0.85、0.09和－0.27，P值均>0.05)，其他各个药物总敏感度呈逐年提高趋势，趋势检验有统计学意义(H：Z=－11.06；S：Z=－6.39；E：Z=－12.39；R：Z=－11.17；Km：Z=－12.60；Ofx：Z=－4.40，P值均<0.05)；其他各个药物总特异度呈逐年提高趋势，趋势检验有统计学意义(H：Z=－3.85；S：Z=－2.14；E：Z=－12.30；R：Z=－3.31；Km：Z=－5.05；Am：Z=－5.43；Cm：Z=－8.90，P值均<0.05)；其他各个药物总重复性呈逐年提高趋势，趋势检验有统计学意义(H：Z=－5.36；S：Z=－9.11；E：Z=－7.76；R：Z=－8.52；Ofx：Z=－3.44，P值均<0.05)；各个药物总一致性呈逐年提高趋势，趋势检验有统计学意义(H：Z=－10.95；S：Z=－5.95；E：Z=－11.87；R：Z=－9.70；Km：Z=－14.11；Am：Z=－3.32；Cm：Z=－5.71；Ofx：Z=－3.40，P值均<0.05)。结论开展熟练度测试工作是提高药敏试验能力的有效方法，对于提高我国结核病实验室药敏试验能力具有很大贡献。长期连续的做好实验室内部质量控制并开展药敏试验培训和熟练度测试工作可使全国结核病实验室药敏试验能力逐年提高。

关键词: 分枝杆菌, 结核, 微生物敏感性试验, 敏感性与特异性

Abstract: Objective To evaluate and analyze the results of nationwide anti-tuberculosis drug susceptibility proficiency testing from 2009 to 2013, and improve the capability of tuberculosis laboratories in China. Methods Natio-nal tuberculosis reference laboratory issued 30 Mycobacterium tuberculosis isolates for the DST to each participating laboratories yearly from 2009 to 2013. The laboratories performed DST for isoniazid(H), streptomycin(S), ethambutol(E), rifampicin(R), kanamycin(Km), amikacin(Am), capreomycin(Cm) and ofloxacin (Ofx) using the proportion method in Lowenstein-Jensen medium, the World Health Organization guideline was strictly followed. All 508 laboratories participated the proficiency testing and reported the results of first line DST, and 445 laboratories reported the results of second line DST. The reported results were checked and compared with the judicial results by national tuberculosis reference laboratory. The evaluation index is sensitivity, specificity, reproducibility and efficiency. The Chi-square test was be used to analyze the results, and the Cochran-Armitage trend test was be used to describe the trend results, significant difference was defined as P<0.05. Results The overall value of sensitivity, specificity, reproducibility and efficiency for each drug was respectively as following: H: 91.88%－97.62%, 92.01%－98.33%, 86.55%－95.27% and 91.40%－97.60%；S: 88.79%－94.14%, 87.59%－91.36%, 77.37%－93.13% and 88.20%－92.45%；E：66.24%－85.17%, 83.22%－97.87%, 63.46%－89.76% and 75.78%－90.80%；R: 78.54%－96.34%, 96.19%－98.07%, 79.11%－95.66% and 90.72%－97.21%；Km: 81.12%－95.46%, 95.35%－98.86%, 94.12%－96.84% and 90.23%－97.77%；Am: 93.14%－98.94%, 96.16%－99.00%, 93.52%－97.94% and 95.59%－98.19%；Cm:52.45%－95.68%, 89.68%－97.85%, 89.48%－92.99% and 89.08%－95.61%；Ofx: 84.75%－94.38%, 96.21%－98.90%, 88.01%－94.41% and 93.01%－96.90%. Except for the specificity of S, reproducibility of Km and Cm was not statistically significant difference between each year(χ² value of 8.49, 4.1, 7.78, respectively, P>0.05）,the difference of overall sensitivity for each drug between each year was statistically significant(H:χ²=134.76；S:χ²=44.12；E:χ²=266.22；R:χ²=256.35；Km:χ²=197.46；Am:χ²=12.16；Cm:χ²=433.50；Ofx:χ²=47.38，P<0.05); the difference of overall specificity for other drug between each year was statistically significant(H:χ²=67.69； E:χ²=439.39；R:χ²=16.61；Km:χ²=94.97；Am:χ²=52.96；Cm:χ²=139.51；Ofx:χ²=11.66，P<0.05);the difference of overall reproducibility for other drug between each year was statistically significant(H:χ²=61.82；S:χ²=127.15；E:χ²=246.49；R:χ²=180.03；Am:χ²=21.65；Ofx:χ²=28.49，P<0.05); the difference of overall efficiency for each drug between each year was statistically significant(H:χ²=162.05；S:χ²=36.58；E:χ²=369.11；R:χ²=152.30；Km:χ²=233.69；Am:χ²=32.55；Cm:χ²=168.79；Ofx:χ²=36.97，P<0.05). While, except for the overall sensitivity of Am and Cm, the overall specificity of Ofx and the overall reproducibility of Km, Am and Cm（Z value of 0.46, 0.99, －0.30, －0.85, 0.09 and －0.27, respectively, P>0.05), the overall sensitivity for other drug showed a trend of increase by year (H:Z=－11.06；S: Z=－6.39；E: Z=－12.39；R: Z=－11.17；Km: Z=－12.60；Ofx: Z=－4.40，P<0.05);the overall specificity for other drug showed a trend of increase by year(H:Z=－3.85；S: Z=－2.14；E: Z=－12.30；R: Z=－3.31；Km: Z=－5.05；Am: Z=－5.43；Cm: Z=－8.90，P<0.05); the overall reprodu-cibility for other drug showed a trend of increase by year(H:Z=－5.36；S: Z=－9.11；E: Z=－7.76；R: Z=－8.52；Ofx: Z=－3.44，P<0.05)；the overall efficiency for each drug showed a trend of increase by year (H:Z=－10.95；S: Z=－5.95；E: Z=－11.87；R: Z=－9.70；Km: Z=－14.11；Am: Z=－3.32；Cm: Z=－5.71；Ofx: Z=－3.40，P<0.05). Conclusion Proficiency testing was an efficient method to improve the capacity and performance of DST, PT has made a great contribution to increase the ability of DST in Chinese TB laboratory network, and continuously conducting the laboratory internal quality control and carrying out personnel training to perform proficiency testing could increase the laboratory capabilities of DST year by year.

Key words: Mycobacterium tuberculosis, Microbial sensitivity tests, , Sensitivity and specificity

宋媛媛，赵冰，夏辉，赵雁林. 2009—2013年全国抗结核药物敏感性试验熟练度测试分析[J]. 中国防痨杂志, 2015, 37(2): 149-156. doi: 10.3969/j.issn.1000-6621.2015.02.007

SONG Yuan-yuan, ZHAO Bing, XIA Hui, ZHAO Yan-lin. Analysis of anti-tuberculosis drug susceptibility proficiency test 2009—2013 in China[J]. Chinese Journal of Antituberculosis, 2015, 37(2): 149-156. doi: 10.3969/j.issn.1000-6621.2015.02.007

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