Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, Kita-ku, Sakai, Osaka, Japan.
Department of Infectious Diseases, Kobe Institute of Health, Kobe, Hyogo, Japan.
J Antimicrob Chemother. 2020 Jul 1;75(7):1722-1725. doi: 10.1093/jac/dkaa109.
Bacterial population kinetics of strains harbouring drug resistance-conferring mutations within a patient often show cryptic resistance in clinical practice. We report a case that showed emergence and dominance of Mycobacterium tuberculosis with uncommon rpoB and gyrA mutations, followed by an rpoC compensatory mutation, during treatment.
A pre-XDR-TB patient showed heteroresistance to rifampicin and levofloxacin during treatment as a result of intermittent self-cessation. WGS was applied to investigate intra-host strain composition using five pairs of isolates from sputum samples.
The subclone in this study possessed rare mutations conferring resistance to rifampicin (rpoB V170F) and levofloxacin (gyrA S91P) and it rapidly outcompeted other subclones during treatment that included levofloxacin but not rifampicin (<7 days). The high-probability compensatory mutation rpoC V483A also emerged and became dominant subsequent to the rpoB V170F mutation.
To the best of our knowledge, this is the first case showing the emergence of such a rare variant that dominated the population within a patient during treatment of TB.
在临床实践中，携带耐药基因突变的菌株的细菌种群动力学通常表现为隐匿性耐药。我们报告了一例在治疗过程中出现并占主导地位的罕见 rpoB 和 gyrA 突变以及 rpoC 补偿性突变的耐多药结核分枝杆菌。
一例预广泛耐药结核患者因间歇性自行停药而在治疗过程中出现异质性耐利福平及左氧氟沙星。应用 WGS 技术从痰标本中 5 对分离株来检测宿主内菌株组成。
本研究中的亚克隆具有罕见的耐利福平（rpoB V170F）和左氧氟沙星（gyrA S91P）的突变，在治疗过程中迅速取代了包括左氧氟沙星但不包括利福平的其他亚克隆（<7 天）。高概率的补偿性突变 rpoC V483A 也随着 rpoB V170F 突变而出现并成为优势突变。
据我们所知，这是首例在治疗结核病期间，此类罕见变异体在患者体内出现并占据主导地位的病例。
