title: Later emergence of acquired drug resistance and its effect on treatment outcome in patients treated with Standard Short-Course Chemotherapy for tuberculosis.
abstract: BACKGROUND
  The failure of current Standard Short-Course Chemotherapy (SCC) in new and previously treated cases with tuberculosis (TB) was mainly due to drug resistance development. But little is known on the characteristics of acquired drug resistant TB during SCC and its correlation with SCC failure. The objective of the study is to explore the traits of acquired drug resistant TB emergence and evaluate their impacts on treatment outcomes.
  
  
  METHODS
  A prospective observational study was performed on newly admitted smear positive pulmonary TB (PTB) cases without drug resistance pretreatment treated with SCC under China's National TB Control Program (NTP) condition from 2008 to 2010. Enrolled cases were followed up through sputum smear, culture and drug susceptibility testing (DST) at the end of 1, 2, and 5 months after treatment initiation. The effect factors of early or late emergence of acquired drug resistant TB , such as acquired drug resistance patterns, the number of acquired resistant drugs and previous treatment history were investigated by multivariate logistic regression; and the impact of acquired drug resistant TB emergence on treatment failure were further evaluated.
  
  
  RESULTS
  Among 1671 enrolled new and previously treated cases with SCC, 62 (3.7%) acquired different patterns of drug resistant TB at early period within 2 months or later around 3-5 months of treatment. Previously treated cases were more likely to develop acquired multi-drug resistant TB (MDR-TB) (OR, 3.8; 95%CI, 1.4-10.4; P = 0.015). Additionally, acquired MDR-TB cases were more likely to emerge at later period around 3-5 months after treatment starting than that of non-MDR-TB mainly appeared within 2 months (OR, 8.3; 95%CI, 1.7-39.9; P = 0.008). Treatment failure was associated with late acquired drug resistant TB emergence (OR, 25.7; 95%CI, 4.3-153.4; P < 0.001) with the reference of early acquired drug resistant TB emergence.
  
  
  CONCLUSIONS
  This study demonstrates that later development of acquired drug resistant TB during SCC is liable to suffer treatment failure and acquired MDR-TB pattern may be one of the possible causes.
authors: Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors: Jingtao
authors: J
authors: Gao
authors: Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors: Yan
authors: Y
authors: Ma
authors: Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors: Jian
authors: J
authors: Du
authors: State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors: Guofeng
authors: G
authors: Zhu
authors: Department of TB Control, Guangzhou Chest Hospital, Guangzhou, Guangdong, China.
authors: Shouyong
authors: S
authors: Tan
authors: Department of TB Control, Tianjin Centers for Disease Control and Prevention, Tianjin, China.
authors: Yanyong
authors: Y
authors: Fu
authors: Department of TB Control, Henan Center for Disease Control and Prevention, Zhengzhou, Henan, China.
authors: Liping
authors: L
authors: Ma
authors: Department of TB Control, Hebei Center for Disease Control and Prevention, Shijiazhuang, Hebei, China.
authors: Lianying
authors: L
authors: Zhang
authors: Department of TB Control, Guangxi Center for Disease Control and Prevention, Nanning, Guangxi, China.
authors: Feiying
authors: F
authors: Liu
authors: Department of TB Control, Chongqing Anti-tuberculosis Institute, Chongqing, China.
authors: Daiyu
authors: D
authors: Hu
authors: Department of TB Control, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, China.
authors: Yanling
authors: Y
authors: Zhang
authors: Department of TB Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors: Xiangqun
authors: X
authors: Li
authors: Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China. liliang69@hotmail.com.
authors: Liang
authors: L
authors: Li
authors: Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China. lq703@hotmail.com.
authors: Qi
authors: Q
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D011446:Prospective Studies; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013307:Streptomycin / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin