Qiao Liu1, Dandan Yang2, Beibei Qiu1, Leonardo Martinez3, Ye Ji1, Huan Song1, Zhongqi Li1, Jianming Wang1. 1. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, PR China. 2. Department of Sexually Transmitted Diseases and AIDS, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, PR China. 3. Division of Infectious Diseases and Geographic Medicine, School of Medicine, Stanford University, Stanford, California, United States of America.
Abstract
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.
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.
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