Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, 102200, China.
BMC Infect Dis. 2021 Apr 8;21(1):330. doi: 10.1186/s12879-021-06024-8.
To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance.
A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers.
MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene.
This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.
探讨左氧氟沙星（LFX）、莫西沙星（MFX）、贝达喹啉（BDQ）、利奈唑胺（LZD）、氯法齐明（CFZ）和德拉马尼（DLM）对来自中国西南地区耐药监测的耐多药结核分枝杆菌（MDR-TB）分离株的药敏活性，并阐明获得性耐药的 MDR-TB 分离株的遗传特征。
2014 年 1 月至 2016 年 12 月，从中国西南地区耐药监测中涂阳肺结核患者中收集了 339 株菌株。采用常规药敏试验测定上述药物对 MDR-TB 的 MIC。用相应的引物对与耐药相关的基因进行扩增。
88 株（26.0%；88/339）分离株表现为 MDR。LFX 的耐药率最高（50.0%；44/88），其次是 MFX（38.6%；34/88）。LZD、CFZ 和 DLM 的耐药率分别为 4.5%（4/88）、3.4%（3/88）和 4.5%（4/88），BDQ 的耐药率最低（2.3%；2/88）。在对 LFX 和 MFX 耐药的 45 株分离株中，gyrA 密码子 94 取代的突变最为常见（34/45，75.6%）。2 株 CFZ-BDQ 交叉耐药株在 Rv0678 基因有突变。4 株 LZD 耐药分离株中，有 2 株 rplC 基因发生突变。4 株 DLM 耐药分离株中，1 株 fbiC 基因 318 密码子发生突变，2 株 ddn 基因 81 密码子发生突变。
本研究为我国 MDR-TB 治疗中新的抗结核药物的应用提供了证据。
