Treatment outcomes of MDR-tuberculosis patients in Brazil: a retrospective cohort analysis

Background: Multidrug-resistant tuberculosis (MDR-TB) is a threat for the global TB epidemic control. Despite existing evidence that individualized treatment of MDR-TB is superior to standardized regimens, the latter are recommended in Brazil, mainly because drug-susceptibility tests (DST) are often restricted to first-line drugs in public laboratories. We compared treatment outcomes of MDR-TB patients using standardized versus individualized regimens in Brazil, a high TB-burden, low resistance setting. Methods: The 2007-2013 cohort of the national electronic database (SITE-TB), which records all special treatments including drug-resistance, was analysed. Patients classified as MDR-TB in SITE-TB were eligible. Treatment outcomes were classified as successful (cure/treatment completed) or unsuccessful (failure/relapse/death/loss to follow-up). The odds for successful treatment according to type of regimen were controlled for demographic and clinical variables. Results: Out of 4029 registered patients, we included 1972 recorded from 2010 to 2012, who had more complete outcome data. The overall success proportion was 60%. Success was more likely in non-HIV patients, sputum-negative at baseline, with unilateral disease and without prior DR-TB. Adjusted for these variables, those receiving standardized regimens had 2.7-fold odds of success compared to those receiving individualized treatments when failure/relapse were considered, and 1.4-fold odds of success when death was included as an unsuccessful outcome. When loss to follow-up was added, no difference between types of treatment was observed. Patients who used levofloxacin instead of ofloxacin had 1.5-fold odds of success. Conclusion: In this large cohort of MDR-TB patients with a low proportion of successful outcomes, standardized regimens had superior efficacy than individualized regimens, when adjusted for relevant variables. In addition to the limitations of any retrospective observational study, database quality hampered the analyses. Also, decision on the use of standard or individualized regimens was possibly not random, and may have introduced bias. Efforts were made to reduce classification bias and confounding. Until higher-quality evidence is produced, and DST becomes widely available in the country, our findings support the Brazilian recommendation for the use of standardized instead of individualized regimens for MDR-TB, preferably containing levofloxacin. Better quality surveillance data and DST availability across the country are necessary to improve MDR-TB control in Brazil.