Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China

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. Author summary Multidrug-resistant tuberculosis (MDR-TB) exacerbates the already serious tuberculosis epidemic, poses a notable threat to global tuberculosis control, and places a considerable burden on developing countries, as treatments for MDR-TB tend to be expensive, of limited efficacy, and toxic. Genotypic determinants of resistance to specific drugs or drug classes offer a rapid and highly specific alternative to phenotypic drug susceptibility testing. Although the relationship between gene mutations and drug resistance has been described previously, the strength of the association of mutations with the treatment outcomes of MDR tuberculosis have not been fully elucidated. The results of our study, which was conducted in a Chinese population, suggest that gene mutations in Mycobacterium tuberculosis may be related to phenotypic drug susceptibility. Mutation of the pncA gene contributes to a poor prognosis and can be applied to predict the treatment outcomes of MDR-TB.

Automated summary

The study found that gene mutations in Mycobacterium tuberculosis may be related to phenotypic drug susceptibility, and mutations in the pncA gene, along with treatment regimen and age, are associated with the treatment outcomes of MDR-TB.