初、复治患者结核分枝杆菌临床分离株对抗结核药物耐药性的分析

Drug Resistance Pattern of the Mycobacterium tuberculosis among Retreantment and New Cases

目的了解专科医院初复治患者的结核分枝杆菌耐药率及耐药谱。方法研究随机选取了来自首都医科大学附属北京胸科医院的500株涂片阳性的初复治肺结核患者痰标本,分离培养后对15种抗结核药物包括利福平异烟肼(INH)、利福平(RFP)、链霉素(Sm)、乙胺丁醇(EMB)、括吡嗪酰胺(PZA)、阿米卡星(Am)、卡那霉素(Km)、卷曲霉素(Cm)、氧氟沙星(Ofx)、左氧氟沙星(Lfx)、莫西沙星(Mfx)、对氨基水杨酸(PAS)、丙硫异烟胺(Pto)、利奈唑胺(Lzd)、乙硫异烟胺(Eto)通过MEGIT 960进行药物敏感试验。结果实验纳入的500例结核分枝杆菌样本,菌种鉴定结果显示71株为NTM,另外有12株培养污染。其余417例菌株进行4种一线抗结核药物(包括INH、RFP、Sm、EMB)的耐药表型实验,耐药率为47.2%(95%CI:42.5%~52.0%),MDR耐药率为28.2%(95%CI:24.4%~33.1%)。复治病例的总耐药率和MDR耐药率的病例发生率均显著高于初治患者(P=0.000)。417株结核分枝杆菌在完成4种一线抗结核耐药表型实验后,采用数字表法按照一定比例筛选了全敏感和耐药株共150例,进行后续11种抗结核药物(包括PZA、Am、Km、Cm、Ofx、Lfx、Mfx、PAS、Pto、Lzd、Eto)的耐药表型实验,5例发生污染,剩余145例结核分枝杆菌对PZA、Am、Km、Cm、Ofx、Lfx、Mfx的复治患者耐药率均显著高于初治患者(P<0.05),对于PAS、Pto、Lzd、Eto 4种药物,初复治患者间差异无统计学意义(P>0.05)。结论本研究发现初复治患者结核分枝杆菌耐药率较高,应进一步加强结核病患者管理。

Objective To investigate the incidence of drug resistance among new and retreatment TB patients from special hospital. Methods Totally 500 smear positive TB patients from June 2013 to December 2014 in Beijing Chest Hospital were enrolled. Phenotypic susceptibilities to cultured isolates were analyzed in 15 anti tuberculosis drugs by MGIT 960, include Isoniazid （INH） , Rifampicin （RFP）, Streptomycin（STR）, Ethambuto （EMB）, Kanamycin （Km）, Amikacin （Am）, Capreomyein （Cm）, Ofloxacin （Ofx）, Levofloxacin （Lfx）, Moxifloxacin （Mfx）, Paza- aminosalicylate （PAS）, Protionamide （Pto）, Linezolid （Lzd）, Ethionamide （Eto）, Pyrazinamide （PZA）. Results A total of 500 TB cases were enrolled. 71 samples among these were NTM infection and 12 samples were contaminted. The rest of 417 of eases infected with Mycobacteriuma, and the rate of drug resistance was 47.2% （192/417） and the MDR rate was 28.2% （120/417）. The retreatment was significantly higher than that of the new in any drug resistance rate and MDR rate （P = 0. 000）. 100 of the retreatment isolates and 50 of the new isolates with Mycobacteriuma were selected to do the drug susceptibility test in 11 subsequent anti tuberculosis drugs （ include ： PZA, Am, Km, Cm, Ofx, Lfx, Mfx, PAS, Pro, Lzd, Eto）. Five cases were contaminated, and in the rest of the eases, 48 was the new and 97was the retreatment. The rate of the drug resistance to PZA, Am, Km, Cm, Ofx, Lfx, Mfx for the retreatment were significantly higher than the new （P 〈 0.05）. The rate of drug resistance to PAS, Pro, Lzd and Eto for the new and reteartment were no markedly differential in statistics. Conclusion This study further confirmed the rate of drug resistance in retreatment cases is higher, and the management of tuberculosis patients should be further strengthened.