Open AccessDrug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China
Author(s) -
Qiao Liu,
Dandan Yang,
Beibei Qiu,
Leonardo Martínez,
Yiqin Ji,
Huan Song,
Zhongqi Li,
Jianming Wang
Publication year - 2021
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0009068
Subject(s) - medicine , odds ratio , extensively drug resistant tuberculosis , drug resistance , bedaquiline , gene mutation , tuberculosis , pyrazinamide , isoniazid , inha , rpob , mycobacterium tuberculosis , mutation , genetics , gene , biology , pathology
Background Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB. Methods We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein–Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43–159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46–124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35–44.35) had a significantly higher risk of poor treatment outcomes. Conclusions These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.