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- Title
Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China.
- Authors
Zhao, Bing; Zheng, Huiwen; Timm, Juliano; Song, Zexuan; Pei, Shaojun; Xing, Ruida; Guo, Yajie; Ma, Ling; Li, Feina; Li, Qing; Li, Yan; Huang, Lin; Teng, Chong; Wang, Ni; Gupta, Aastha; Juneja, Sandeep; Huang, Fei; Zhao, Yanlin; Ou, Xichao
- Abstract
Background: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. Methods: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. Results: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. Conclusions: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.
- Subjects
CHINA; MYCOBACTERIUM tuberculosis; DRUG resistance; TUBERCULOSIS; GENOTYPES
- Publication
Annals of Clinical Microbiology & Antimicrobials, 2024, Vol 23, Issue 1, p1
- ISSN
1476-0711
- Publication type
Article
- DOI
10.1186/s12941-024-00697-0