结核分枝杆菌临床分离株对四种注射用抗结核药物耐药及交叉耐药分析

Analysis on drug resistance and cross resistance of Mycobacterium tuberculosis isolated from clinical samples to four injectable antituberculous drugs

目的探讨链霉素(S)、卡那霉素(Km)、阿米卡星(Am)和卷曲霉素(Cm)对结核分枝杆菌的耐药及交叉耐药情况,为耐药结核病的化学治疗提供理论依据。方法对首都医科大学附属北京胸科医院2004年1月至2010年12月间4247株临床分离株的药物敏感试验结果进行分析。采用绝对浓度法进行药物敏感试验。4种药物之间总耐药率的差异采用配对χ2检验及χ2分割法,以P<0.007 14为差异有统计学意义。4种药物之间交叉耐药率的差异采用两个样本率比较的χ2检验,以P<0.05为差异具有统计学意义。结果4247份临床分离株标本中,S的耐药率为45.11%(1916/4247),Km的耐药率为17.93%(718/4005),Am的耐药率为19.02%(792/4164),Cm的耐药率为9.44%(401/4247)。经配对χ2检验,Cm与S、Am、Km之间耐药率差异有统计学意义,χ2值分别为1349.34、281.54、193.16,P值均小于0.007 14。经配对χ2检验,S与Am、Km之间耐药率差异有统计学意义,χ2值分别为821.10、869.28,P值均小于0.007 14。经配对χ2检验,Am与Km之间耐药率差异有统计学意义,χ2值为13.98,P值小于0.007 14,耐药率从高到低依次为S、Am、Km和Cm。S在其他3种药物的耐药株中的耐药率分别为82.59%(耐Km株,593/718)、77.78%(耐Am株,616/792)、76.81%(耐Cm株,308/401),χ2值分别为502.959、453.911、626.654,P值均小于0.05。Km在另外3种药物耐药株中的耐药率分别为33.13%(耐S株,593/1790)、83.31%(耐Am株,634/761)、67.89%(耐Cm株,260/383),χ2值分别为502.959、12.079、100.536,P值均小于0.05。Am在另外3种药物耐药株的耐药率分别为32.78%(耐S株,616/1879)、89.55%(耐Km株,634/708)、77.95%(耐Cm株,304/390),χ2值分别为453.911、12.079、163.761,P值均小于0.05。Cm在其他3种药物的耐药株中的耐药率分别为16.08%(耐S株,308/1916)、36.21%(耐Km株,260/718)和38.38%(耐Am株,304/792),χ2值分别为626.654、100.536、163.761,P值均小于0.05。结论4种注射用抗结核药物的耐药率从高到低依次为S、Am、Km和Cm。4种药物之间均表现出交叉耐药,但程度不同。S与其他3种药物之间为单向耐药,Km和Am两个药物之间近似完全交叉耐药,Cm是其他3种药物耐药时的选择药物。

Objective To investigate the drug resistance and the cross resistance of Mycobacterium tuberculosis isolated from clinical samples to streptomycin （S）, kanamycin （Kin）, amikacin （Am） and capreomycin （Cm） and to provide scientific evidences for clinical treatment of drug resistance tuberculosis. Methods A retrospective study was adopted to analyze the results of drug susceptibility testing（DST） with absolute concentration method of 4247 isolates from patients with tuberculosis in Beijing Chest Hospital from Jan. 2004 to Dec. 2010. Mathed Chi-square test and partition of chi-square were applied for the overall drug resistant rate analysis, while chi-square test was applied to compare the cross resistance to 4 injectable antituberculous drugs. Results The drug resistant rates to the four drugs were 45. ll%（S, 1916/4247）, 17.93%（Km, 718/4005）, 19.02%（Am,792/4164） and 9.44%（Cm,401/4247） among 4247 resistant isolates respectively. The differences were statistically significant by matched ;χ^2-test and partitions of χ^2 method. The values of χ^2 were 1349.34 （Cm/S）, 281.54 （Cm/Am） and 193.16 （Cm/Km） （P〈0. 007 14） respectively. For the drug resistant rates of S/Am and S/Km, the values of χ^2 were 821.10 （S/Am） and 869.28 （S/Km） （P〈0. 007 14） respectively. The value of χ^2 was 13.98 （Am/Km） （P〈 0. 007 14）. The drug resistant rates sequencing from up to down were S, Am, Km and Cm. The drug resistant rates to S among the other 3 drug-resistance isolates were 82.59%（Km resistant isolates, 593/718）, 77.78%（Am resist- ant isolates, 616/792） and 76.81 % （Cm resistant isolates, 308/401） respectively. The values of χ^2 were 502. 959,453. 911 and 626. 654 （P〈0.05）. The drug resistant rates to Km among the other 3 drug-resistance isolates were 33.13%（S resistant isolates, 593/1790）, 83.31%（Am resistant isolates, 634/761） and 67.89%（Cm resistant isolates, 260/383） respectively. The values of χ^2 were 502. 959, 12. 079 and 100. 536 （P〈0.05）. The drug resistant rates to Am among the other 3 drug-resistance isolates were 32.78%（S resistant isolates, 616/1879）, 89.55%（Km resistant isolates, 634/708） and 77.95%（Cm resistant isolates, 304/390） respectively. The values of χ^2 were 453. 911, 12. 079 and 163. 761 （P〈0.05）. The drug resistant rates to Cm among the other three drug resistance isolates were 16.08%（S resistant isolates, 308/1916）, 36.21%（Km resistant isolates, 260/718） and 38.38%（Am resistant isolates, 304/792） respectively. The values of χ^2 were 626. 654, 100. 536 and 163. 761 （P〈0.05）.Conclusion The drug resistant rates sequencing from up to down of four injectable antituberculous drugs are streptomycin, amikacin, kanamycin and capreomycin. There are cross resistances among these four drugs with different levels. Streptomycin is unidirectional resistant to the other three drugs. Kanamycin and amikacin are almost full cross-resistant. Capreomycin is the candidate drug when the other three drugs are resistant.