RATIONALE: Few large-scale studies have investigated multidrug-resistant tuberculosis (MDR-TB) treatment outcomes relative to drug-resistance patterns. OBJECTIVES: To assess the impact of additional drug resistances on treatment outcomes and long-term survival in a large HIV-negative MDR-TB cohort. METHODS: Treatment outcomes and long-term survival of patients with MDR-TB newly diagnosed or retreated in 2000 to 2002 were retrospectively analyzed based on drug-resistance patterns after 5-8 years of follow-up. MEASUREMENTS AND MAIN RESULTS: Of 1,407 patients with MDR-TB, 75 (5.3%) had extensively drug-resistant TB (XDR-TB(re)) by the revised definition; 159 (11.3%) had ofloxacin-resistant pre-XDR-TB (pre-XDR-TB(o)); and 117 (8.3%) had second-line injectable drug (SLID)-resistant pre-XDR-TB (pre-XDR-TB(s)). Patients with XDR-TB(re) showed the lowest treatment success rate (29.3%) and the poorest long-term survival, and XDR-TB(re) was more strongly associated with long-term mortality than XDR-TB as originally defined (hazards ratio [HR], 3.15; 95% confidence interval [CI], 2.06-4.83; P < 0.001 vs. HR, 2.15; 95% CI, 1.49-3.09; P < 0.001). Patients with either form of pre-XDR-TB showed poorer cumulative survival than those with ofloxacin-susceptible/SLID-susceptible MDR-TB (P < 0.05 for each comparison). Although streptomycin susceptibility did not affect the treatment outcomes of patients with pre-XDR-TB, streptomycin-resistant pre-XDR-TB was more strongly associated with long-term mortality than ofloxacin-susceptible/SLID-susceptible MDR-TB (HR, 2.17; 95% CI, 1.22-3.84; P < 0.008 for pre-XDR-TB(o); and HR, 2.69; 95% CI, 1.40-5.16; P = 0.003 for pre-XDR-TB(s)). CONCLUSIONS: The revised XDR-TB definition is appropriate for defining patients with MDR-TB with the poorest outcomes. Both pre-XDR-TB(o) and pre-XDR-TB(s) were independently associated with poor long-term survival in patients with MDR-TB. SM susceptibility was linked to better survival in patients with pre-XDR-TB.
RATIONALE: Few large-scale studies have investigated multidrug-resistant tuberculosis (MDR-TB) treatment outcomes relative to drug-resistance patterns. OBJECTIVES: To assess the impact of additional drug resistances on treatment outcomes and long-term survival in a large HIV-negative MDR-TB cohort. METHODS: Treatment outcomes and long-term survival of patients with MDR-TB newly diagnosed or retreated in 2000 to 2002 were retrospectively analyzed based on drug-resistance patterns after 5-8 years of follow-up. MEASUREMENTS AND MAIN RESULTS: Of 1,407 patients with MDR-TB, 75 (5.3%) had extensively drug-resistant TB (XDR-TB(re)) by the revised definition; 159 (11.3%) had ofloxacin-resistant pre-XDR-TB (pre-XDR-TB(o)); and 117 (8.3%) had second-line injectable drug (SLID)-resistant pre-XDR-TB (pre-XDR-TB(s)). Patients with XDR-TB(re) showed the lowest treatment success rate (29.3%) and the poorest long-term survival, and XDR-TB(re) was more strongly associated with long-term mortality than XDR-TB as originally defined (hazards ratio [HR], 3.15; 95% confidence interval [CI], 2.06-4.83; P < 0.001 vs. HR, 2.15; 95% CI, 1.49-3.09; P < 0.001). Patients with either form of pre-XDR-TB showed poorer cumulative survival than those with ofloxacin-susceptible/SLID-susceptible MDR-TB (P < 0.05 for each comparison). Although streptomycin susceptibility did not affect the treatment outcomes of patients with pre-XDR-TB, streptomycin-resistant pre-XDR-TB was more strongly associated with long-term mortality than ofloxacin-susceptible/SLID-susceptible MDR-TB (HR, 2.17; 95% CI, 1.22-3.84; P < 0.008 for pre-XDR-TB(o); and HR, 2.69; 95% CI, 1.40-5.16; P = 0.003 for pre-XDR-TB(s)). CONCLUSIONS: The revised XDR-TB definition is appropriate for defining patients with MDR-TB with the poorest outcomes. Both pre-XDR-TB(o) and pre-XDR-TB(s) were independently associated with poor long-term survival in patients with MDR-TB. SM susceptibility was linked to better survival in patients with pre-XDR-TB.
Authors: Kelly E Dooley; Carole D Mitnick; Mary Ann DeGroote; Ekwaro Obuku; Vera Belitsky; Carol D Hamilton; Mamodikoe Makhene; Sarita Shah; James C M Brust; Nadza Durakovic; Eric Nuermberger Journal: Clin Infect Dis Date: 2012-05-21 Impact factor: 9.079
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Authors: Sharon Y Wong; Jong Seok Lee; Hyun Kyung Kwak; Laura E Via; Helena I M Boshoff; Clifton E Barry Journal: Antimicrob Agents Chemother Date: 2011-03-28 Impact factor: 5.191
Authors: Keertan Dheda; Tawanda Gumbo; Neel R Gandhi; Megan Murray; Grant Theron; Zarir Udwadia; G B Migliori; Robin Warren Journal: Lancet Respir Med Date: 2014-03-24 Impact factor: 30.700