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Objective: To analyze tuberculosis treatment outcomes and their predictors. Methods: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. Results: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72%, 19%, 2%, and 6%, respectively. Changes in the treatment regimen due to adverse events occurred in 8%. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethamb utol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). Conclusions: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.Keywords: Tuberculosis; HIV; Rifampin; Drug toxicity; Risk factors; Medication adherence. ResumoObjetivo: Analisar os desfechos do tratamento da tuberculose e seus preditores. Métodos: Estudo longitudinal de coorte de pacientes com tuberculose tratados entre 2004 e 2006 no Instituto de Pesquisa Evandro Chagas, na cidade do Rio de Janeiro. As razões de risco ajustadas (RRa) dos preditores foram estimadas. Resultados: Foram incluídos 311 pacientes. As taxas de cura, de abandono, de mortalidade e de falha terapêutica foram, respectivamente, 72%, 19%, 6% e 2%. A troca de regime terapêutico por eventos adversos foi necessária em 8%. O alcoolismo (RRa, 0,30), uso do regime estreptomicina+etambutol+ofloxacina (SEO; RRa, 0,32), infecção por HIV sem tratamento antirretroviral (TARV; RRa, 0,36) e o uso do regime rifampicina+isoniazida+pirazinamida+etambutol (RRa, 0,58) reduziram a probabilidade de cura. A faixa etária mais jovem (RRa, 3,84) e o alcoolismo (RRa, 1,76) aumentaram a probabilidade do abandono. Não foi possível determinar as RRa para os demais desfechos devido a suas baixas prevalências. Entretanto, medidas do risco relativo (RR) identificaram os seguintes potenciais preditores do óbito: uso de esquema SEO (RR,1...

Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported.

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206

BackgroundThe combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment.MethodsAdults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment.Results121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450–600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were similar (5/62 [8%] in the investigational arm vs. 6/59 [10%, p = 0.76] in the control arm).ConclusionFor intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide, a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus standard dose rifampin.Trial Registrationwww.ClinicalTrials.gov NCT00728507

A more comprehensive approach is needed to manage MDRTB, addressing early diagnostic, improving adhesion, and comorbidities, mainly HIV infection and drug abuse. The latest generation quinolones have an important effect in improving survival in MDRTB.

INTRODUÇÃOO comprometimento pleural representa a forma mais freqüente da tuberculose (TB) extrapulmonar. Freqüências variáveis são observadas em diferentes países, de acordo com a prevalência da TB e da sorologia positiva para o vírus da imunodeficiência humana (HIV).(1)A TB pleural pode ser uma manifestação tanto da forma primária da doença (primo-infecção) quanto da reativação de uma infecção latente pelo Mycobacterium tuberculosis. Em ambas a TB pleural está freqüentemente associada à forma pulmonar.(2) Nos países com alta prevalência, a TB ocorre mais em jovens como manifestação da TB primária, enquanto que nos países com baixa pre- RESUMOO derrame pleural tuberculoso pode ser devido a uma manifestação da forma primária da doença ou da reativação de uma infecção latente pelo M. tuberculosis. Os avanços nos métodos laboratoriais contribuíram sobremaneira para um melhor diagnóstico e para a compreensão da fisiopatologia desta doença. No entanto, embora o derrame pleural predominante linfocítico seja indicativo de tuberculose em nosso meio, uma rotina de abordagem diagnóstica deve ser instituída a fim de orientar o tratamento precoce e evitar seqüelas.Descritores: Tuberculose pleural/fisiopatologia; Derrame pleural/fisiopatologia; Tuberculose pleural/epidemiologia; Derrame pleural/epidemiologia; Biopsia ABSTRACTTuberculous pleural effusion is a common manifestation of the primary form of the disease or consequence of the reactivation of a latent infection due to the M. tuberculosis. Advances in the laboratory methods have contributed to better diagnose and understand the pathophysiology of the effusion secondary to tuberculosis. However, although a predominant lymphocytic pleural effusion is suspicious of tuberculosis, a diagnostic routine shall be instituted to orient treatment and prevent undesirable sequels.Keywords: Tuberculosis, pleural/physiopathology; Pleural effusion/physiopathology; Tuberculosis, pleural/epidemiology; Pleural effusion/epidemiology; Biopsy valência ela atinje mais a população idosa, como conseqüência da reativação de um foco de infecção latente, caracterizando a reativação endógena da doença. EPIDEMIOLOGIAEm todo o mundo, cerca de nove milhões de pessoas desenvolvem TB a cada ano. Aproximadamente 80% delas vivem em 22 diferentes países, sendo que o Brasil ocupa o 15º lugar, com cerca de 80 mil casos notificados a cada ano. Em alguns estados, a incidência da doença supera 100 casos por 100 mil habitantes. Além disto, há uma estimativa de 50 milhões de pessoas infectadas.

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