Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed. The effectiveness of clofazimine was assessed by comparing the treatment outcomes of patients undergoing clofazimine-containing regimens against those undergoing clofazimine-free regimens and its safety by describing clofazimine-attributed adverse events. A total of 1446 patients were treated with clofazimine-containing regimens and 1096 with pyrazinamide-containing regimens.Although success rates were similar in patients treated with clofazimine those treated with pyrazinamide (880 out of 1446, 60.9%, 708 out of 1096, 64.6%; p=0.054), clofazimine-treated cases exhibited higher death rates due to tuberculosis than pyrazinamide-treated ones (314 out of 1446, 21.7%, 120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%, 95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%, 151 out of 1096, 13.8%). No relevant differences were detected when comparing adverse events in patients treated with clofazimine-containing regimens to those treated with clofazimine-free regimens. However, the incidence of side-effects was less than previously reported (gastro-intestinal complaints: 10.5%; hyper-pigmentation: 50.2%; neurological disturbances: 9-13%).

The difficulties in managing multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant (XDR) TB are well known. The regimens are very expensive, often toxic, and require up to 24 months to achieve an acceptable probability of success [1-3]. Based on successful experiences in different settings, the World Health Organization (WHO) recently provided recommendations on the prescription of a new "shorter" regimen to treat MDR-TB, which is also known as the "Bangladesh regimen" [4-8]. The regimen is composed of kanamycin, moxifloxacin (gatifloxacin being the fluoroquinolone originally used in the "Bangladesh" regimen), prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol for an initial period (4-6 months), then moxifloxacin, clofazimine, pyrazinamide and ethambutol for the continuation phase (5 months) [8]. The regimen has interesting characteristics. It is considerably cheaper than the traditional "long" regimen (USD20 000 or more), has a much shorter duration (9-12 months), and achieves relapse-free success rates exceeding 90% (the positive outcomes of the traditional "longer" regimen are on the order of 50-60%) [8]. The regimen is indicated for patients not previously treated with second-line drugs and unlikely to be resistant to them. WHO recommended the extensive use of rapid molecular testing for the detection of resistances to second-line drugs (Geno Type MTBDRsl) to allow prescription of this regimen to the patients who can benefit from it without risk of developing further drug resistance [8]. Recently, several contributions tried to estimate the proportion of eligible patients in different geographical settings. This ranged from ∼10% in Europe to 50% in Pakistan [9-12]. No countrywide information in this sense is available from Latin America. As part of an ongoing collaboration project between the European Respiratory Society (ERS), the Brazilian Society of Respiratory Medicine (SBPT) and the Brazilian National TB Programme, we analysed the information provided by the Brazilian national register (SITE TB), including all patients needing a treatment different from the standard 6 month regimen for (drug-susceptible) TB cases. The aim of this study is to describe the resistance profile of the drugs composing the "shorter" regimen among MDR-TB cases diagnosed between 2000 and 2015. In Brazil, the MDR-TB regimen is standardised in the majority of cases [13]. Originally, it contained clofazimine and ofloxacin, but in 2006 pyrazinamide replaced clofazimine and in 2010 levofloxacin replaced ofloxacin as the backbone fluoroquinolone (5 months with amikacin or streptomycin (five times a week for 1 month and three times a week for the following 4 months), ethambutol, levofloxacin, pyrazinamide and terizidone, and 12 months with ethambutol, levofloxacin and terizidone). On this basis we analysed, separately, individuals enrolled between 2000 and 2010 from those treated between 2011 and 2015. Absolute frequencies (percentages) and medians (interquartile ranges; IQR...

The Special Tuberculosis Treatment Information System (SITE-TB) arose mainly from the need to routinely monitor all persons with drug-resistant tuberculosis (DR-TB) in Brazil, as well as to qualify tuberculosis' drug control. Developed by the Professor Hélio Fraga Reference Center and the Management Sciences for Health/Brazil Project, this online system was implemented in 2013 in all Brazilian states. In addition to DR-TB, the system registers people with drug-sensitive tuberculosis with special regimen indications, and those with nontuberculous mycobacterial infections identified by differential diagnosis of tuberculosis. All confirmed tuberculosis cases should be notified on the Notifiable Diseases Information System (SINAN). In situations where treatment with special regimens is necessary, the case is closed on SINAN and notified on SITE-TB. Professionals from tuberculosis reference centers report and monitor these cases on the system, as well as manage tuberculosis' drugs.

Background Treatment outcomes were evaluated of a cohort of new pulmonary tuberculosis (TB) cases that were rifampicin resistant, multidrug-resistant, or extensively resistant during 2013 and 2014 in Brazil. The objective of this study is to identify factors associated with unfavorable treatment outcomes for drug-resistant TB cases. Methods The Brazilian Special Tuberculosis Treatment Information System (SITE-TB) was the main data source. The independent variables were classified into four blocks (block I: individual characteristics; block II: clinical characteristics and proposed treatment; block III: treatment follow-up characteristics; and block IV: TB history). The category of successful therapeutic outcome was compared with lost to follow-up, failure, and death. Considering the multiple outcomes as the dependent variable, the odds ratios (OR) and its respective 95% confidence interval (95% CI) were estimated by multinomial logistic regression. Results After applying the exclusion criteria, 980 (98.8%) individuals were included in the study. Of these, 621 (63.4%) had successful treatment, 163 (16.6%) lost to follow-up, 76 (7.8%) failed, and 120 (12.2%) died. Important factors associated with lost to follow-up in the final model included use of illicit drugs (OR = 2.5 95% CI: 1.57–3.82). Outcome failure was associated with having disease in both lungs (OR = 2.0; 95% CI: 1.09–3.62) and using more than one or not using injectable medication (OR = 2.8; 95% CI: 1.05–7.69). Major factors for the death outcome were at least 60 years old (OR = 3.4; 95% CI: 1.90–6.03) and HIV positive (OR = 2.7; 95% CI: 1.45–4.83). Conclusions The factors associated with unfavorable treatment outcomes were different. Some of these factors are specific to each outcome, which reflects the complexity of providing care to these individuals.