Lemus Dihadenys, Echemendía Miguel, Díaz Raúl, Llanes María J, Suárez Lourdes, Marrero Antonio
Pedro Kourí Tropical Medicine Institute. Havana, Cuba.
MEDICC Rev. 2017 Jan;19(1):10-15. doi: 10.37757/MR2017.V19.N1.3.
INTRODUCTION Systematic surveillance of antituberculosis drug resistance allows identification of multidrug-resistant and extensively drug-resistant isolates of Mycobacterium tuberculosis. Surveillance studies of antituberculosis drug resistance systematically conducted in Cuba for over 15 years have revealed low circulation of multidrug-resistant tuberculosis, under 1% in new cases. OBJECTIVE Characterize antituberculosis drug resistance in isolates of M. tuberculosis recovered from patients with pulmonary tuberculosis in Cuba in 2012-2014. METHODS The nitrate reductase assay was used to test 997 isolates of M. tuberculosis for sensitivity to isoniazid and rifampicin. Isolates identified as multidrug resistant were tested for sensitivity to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, amikacin, kanamycin and capreomycin by the proportion method, as well as genetic resistance mutations in rpoB, katG, inhA, gyrA, rrs and embB genes, using GenoType MTBDRplus and MTBDRsl commercial kits. RESULTS Some 95.6% of isolates from new cases and 89.6% of isolates from previously treated patients were sensitive to isoniazid and rifampicin. Multidrug resistance was found in 0.8% of new and 5.2% of previously treated patients, a statistically significant difference. One extensively drug-resistant isolate was detected among previously treated cases. All isolates examined with the molecular method had mutations in the rpoB gene, which is associated with resistance to rifampicin; only seven showed mutations in the katG gene and one in the inhA gene associated with isoniazid resistance. In one isolate, we found mutations in both gyrA and rrs genes, which are associated with resistance to fluoroquinolones and second-line injectable drugs and therefore, extensive resistance. CONCLUSIONS Results corroborate the low frequency of multidrug-resistant and extensively resistant M. tuberculosis strains in Cuba and highlight the need for continuous improvement of surveillance of antituberculosis drug resistance in Cuba. KEYWORDS Mycobacterium tuberculosis, multidrug resistance, extensively drug-resistant tuberculosis, Cuba.
引言 对抗结核药物耐药性进行系统监测有助于识别结核分枝杆菌的耐多药和广泛耐药菌株。古巴系统开展抗结核药物耐药性监测研究已超过15年，结果显示耐多药结核病的传播率较低，新发病例中该比例低于1%。
目的 对2012 - 2014年在古巴从肺结核患者中分离出的结核分枝杆菌菌株的抗结核药物耐药性进行特征分析。
方法 采用硝酸还原酶试验检测997株结核分枝杆菌对异烟肼和利福平的敏感性。对鉴定为耐多药的菌株，采用比例法检测其对异烟肼、利福平、链霉素、乙胺丁醇、氧氟沙星、阿米卡星、卡那霉素和卷曲霉素的敏感性，并使用GenoType MTBDRplus和MTBDRsl商业试剂盒检测rpoB、katG、inhA、gyrA、rrs和embB基因中的耐药基因突变情况。
结果 新发病例中约95.6%的菌株和既往治疗患者中89.6%的菌株对异烟肼和利福平敏感。耐多药在新发病例中的比例为0.8%，在既往治疗患者中的比例为5.2%，差异具有统计学意义。在既往治疗病例中检测到1株广泛耐药菌株。所有采用分子方法检测的菌株在与利福平耐药相关的rpoB基因中均有突变；仅7株在与异烟肼耐药相关的katG基因中有突变，1株在inhA基因中有突变。在1株菌株中，我们发现gyrA和rrs基因均有突变，这与对氟喹诺酮类药物和二线注射用药物耐药相关，因此该菌株具有广泛耐药性。
结论 结果证实古巴耐多药和广泛耐药结核分枝杆菌菌株的频率较低，并强调古巴需要持续改进抗结核药物耐药性监测工作。
关键词 结核分枝杆菌；耐多药；广泛耐药结核病；古巴
