title: Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.
abstract: BACKGROUND
  Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.
  
  
  METHODS
  To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC.
  
  
  RESULTS
  In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance.
  
  
  CONCLUSIONS
  Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: J Peter
authors: JP
authors: Cegielski
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Tracy
authors: T
authors: Dalton
authors: National Institute of Health, Lima, Peru.
authors: Martin
authors: M
authors: Yagui
authors: Department of Disease Control, Ministry of Public Health, Bangkok, Thailand.
authors: Wanpen
authors: W
authors: Wattanaamornkiet
authors: Vladimir Oblast Tuberculosis Dispensary, Russian Federation.
authors: Grigory V
authors: GV
authors: Volchenkov
authors: National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Laura E
authors: LE
authors: Via
authors: Medical Research Council, Pretoria, Republic of South Africa.
authors: Martie
authors: M
authors: Van Der Walt
authors: Tropical Disease Foundation, Manila, Republic of the Philippines.
authors: Thelma
authors: T
authors: Tupasi
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Sarah E
authors: SE
authors: Smith
authors: Medical Research Council, Pretoria, Republic of South Africa.
authors: Ronel
authors: R
authors: Odendaal
authors: Riga East University Hospital Centre of Tuberculosis and Lung Diseases, Latvia.
authors: Vaira
authors: V
authors: Leimane
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Charlotte
authors: C
authors: Kvasnovsky
authors: Vladimir Oblast Tuberculosis Dispensary, Russian Federation.
authors: Tatiana
authors: T
authors: Kuznetsova
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Ekaterina
authors: E
authors: Kurbatova
authors: Tartu University Hospital, Estonia.
authors: Tiina
authors: T
authors: Kummik
authors: Riga East University Hospital Centre of Tuberculosis and Lung Diseases, Latvia.
authors: Liga
authors: L
authors: Kuksa
authors: Tartu University Hospital, Estonia.
authors: Kai
authors: K
authors: Kliiman
authors: Orel Oblast Tuberculosis Dispensary, Russian Federation.
authors: Elena V
authors: EV
authors: Kiryanova
authors: Korean Institute of Tuberculosis, Seoul, Republic of Korea.
authors: HeeJin
authors: H
authors: Kim
authors: Korean Institute of Tuberculosis, Seoul, Republic of Korea.
authors: Chang-ki
authors: CK
authors: Kim
authors: Orel Oblast Tuberculosis Dispensary, Russian Federation.
authors: Boris Y
authors: BY
authors: Kazennyy
authors: Taiwan Centers for Disease Control, Taipei.
authors: Ruwen
authors: R
authors: Jou
authors: Taiwan Centers for Disease Control, Taipei.
authors: Wei-Lun
authors: WL
authors: Huang
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Julia
authors: J
authors: Ershova
authors: Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow.
authors: Vladislav V
authors: VV
authors: Erokhin
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Lois
authors: L
authors: Diem
authors: Socios en Salud Sucursal, Lima, Peru.
authors: Carmen
authors: C
authors: Contreras
authors: International Tuberculosis Research Center, Changwon Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Sang Nae
authors: SN
authors: Cho
authors: Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow.
authors: Larisa N
authors: LN
authors: Chernousova
authors: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Michael P
authors: MP
authors: Chen
authors: Tropical Disease Foundation, Manila, Republic of the Philippines.
authors: Janice Campos
authors: JC
authors: Caoili
authors: Socios en Salud Sucursal, Lima, Peru.
authors: Jaime
authors: J
authors: Bayona
authors: Department of Disease Control, Ministry of Public Health, Bangkok, Thailand.
authors: Somsak
authors: S
authors: Akksilp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011446:Prospective Studies; D012641:Selection, Genetic; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: Green Light Committee; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis; tuberculosis