Du Jian, Gao Jingtao, Yu Yanhong, Li Qingfeng, Bai Guanghong, Shu Wei, Gao Mengqiu, Liu Yuhong, Wang Lu, Wang Yufeng, Xue Zhongtan, Huo Fengmin, Li Liang, Pang Yu
Clinical Center on TB, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Tuberculosis Laboratory, Shenyang Tenth People's Hospital (Shenyang Chest Hospital), Shenyang, China.
Front Microbiol. 2021 May 3;12:655653. doi: 10.3389/fmicb.2021.655653. eCollection 2021.
In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed using Sanger sequencing to detect mutations conferring LZD resistance. Of 277 patients in our cohort, 115 (115/277, 41.5%) with prior LZD exposure yielded 19 (19/277, 6.9%) isolates exhibiting LZD resistance. The LZD resistance rate of LZD-exposed group isolates significantly exceeded the corresponding rate for non-exposed group isolates ( = 0.047). Genetic mutations were observed in 10 (52.6%, 10/19) LZD-resistant isolates, of which a Cys154Arg (36.8%, 7/19) substitution within ribosomal protein L3 was most prevalent. Analysis of sequential positive cultures obtained from 81 LZD-treated patients indicated that cultured organisms obtained from most patients (85.2%, 69/81) retained original LZD MIC values; however, organisms cultured later from two patients exhibited significantly increased MIC values that were attributed to the substitution T460C. Overall, LZD resistance was detected in 6.9% of patients of an MDR-TB cohort in China. Low rate of acquired LZD resistance was noted in MDR-TB treated with BDQ-LZD combination.
在这项中国的回顾性研究中，我们旨在：（1）确定耐多药结核病（MDR-TB）感染患者中利奈唑胺（LZD）耐药的患病率；（2）监测抗结核治疗期间LZD药敏的动态变化；（3）探索LZD耐药的分子机制。在中国13家结核病专科医院中，共有277例接受含贝达喹啉（BDQ）方案治疗的MDR-TB患者纳入本研究。采用最低抑菌浓度（MIC）法测定LZD和BDQ药敏率，然后使用桑格测序法分析患者分离株的DNA序列，以检测赋予LZD耐药性的突变。在我们的队列中的277例患者中，115例（115/277，41.5%）曾接触过LZD，其分离株中有19例（19/277，6.9%）表现出LZD耐药。LZD暴露组分离株的LZD耐药率显著高于未暴露组分离株的相应耐药率（ = 0.047）。在10例（52.6%，10/19）LZD耐药分离株中观察到基因突变，其中核糖体蛋白L3内的Cys154Arg替代（36.8%，7/19）最为常见。对81例接受LZD治疗患者的连续阳性培养物分析表明，大多数患者（85.2%，69/81）培养的微生物保留了原始LZD MIC值；然而，后来从两名患者培养的微生物表现出显著增加的MIC值，这归因于T460C替代。总体而言，在中国MDR-TB队列中，6.9%的患者检测到LZD耐药。在用BDQ-LZD联合治疗的MDR-TB中，获得性LZD耐药率较低。
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