Objetivo: Verificar a detecção precoce de ototoxicidade causada pelo uso de amicacina numa população tratada para tuberculose multirresistente (TBMR) por meio da realização de três testes distintos: audiometria tonal liminar (ATL), audiometria de altas frequências (AAF) e pesquisa de emissões otoacústicas por produto de distorção (EOAPD). Métodos: Estudo longitudinal de coorte prospectiva incluindo pacientes de ambos os sexos, com idade entre 18 e 69 anos, com diagnóstico de TBMR pulmonar e que necessitaram utilizar amicacina por seis meses em seu esquema medicamentoso antituberculose pela primeira vez. A avaliação auditiva foi realizada antes do início do tratamento e depois de dois e seis meses do início do tratamento. A análise dos resultados foi realizada por meio de análise estatística sequencial. Resultados: Foram incluídos 61 pacientes, mas a população final foi constituída de 10 pacientes (7 homens e 3 mulheres), em razão da análise sequencial. Ao se comparar os valores das respostas dos testes com aqueles encontrados na avaliação basal, foram verificadas mudanças nos limiares auditivos compatíveis com ototoxicidade após dois meses de tratamento através da AAF e após seis meses de tratamento através da ATL. Entretanto, essas mudanças não foram verificadas através da pesquisa de EOAPD. Conclusões: Ao se considerar o método estatístico utilizado nessa população, é possível concluir que mudanças nos limiares auditivos foram associadas ao uso da amicacina no período de seis meses por meio de AAF e ATL e que a pesquisa de EOAPD não se mostrou eficiente na identificação dessas mudanças.

Keywords: Tuberculosis; Hearing loss; Aminoglycosides/toxicity.

Objective: To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). Methods: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. Results: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. Conclusions: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

Keywords: Nontuberculous mycobacteria/classification; Nontuberculous mycobacteria/drug effects; Lung diseases.

Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 [95% CI: 1.3-9.86]; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 [95% CI: 1.57-25.21]; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

Keywords: Tuberculosis; Treatment outcome; Smoking.

Objective: The incidence of lung disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. In Brazil, there are few studies about nontuberculous mycobacterial lung disease (NTMLD), and its prevalence is yet to be known. Our objective was to determine the specific etiology of the disease in the state of Rio Grande do Sul, Brazil, as well as the frequency and diversity of NTM species in our sample of patients. Methods: This is a retrospective analysis of the medical records of patients diagnosed with NTMLD treated in a referral center located in the city of Porto Alegre, Brazil, between 2003 and 2013. Results: Our sample comprised 100 patients. The most prevalent NTM species were Mycobacterium avium complex (MAC), in 35% of the cases; M. kansasii, in 17%; and M. abscessus, in 12%. A total of 85 patients had received previous treatment for tuberculosis. Associated conditions included structural abnormalities in the lungs, such as bronchiectasis, in 23% of the cases; COPD, in 17%; and immunosuppressive conditions, such as AIDS, in 24%. Conclusions: MAC and M. kansasii were the most prevalent species involved in NTMLD in the state, similarly to what occurs in other regions of Brazil. Data on regional epidemiology of NTMLD, its specific etiology, and associated conditions are essential to establish appropriate treatment, since each species requires specific regimens. Most patients with NTMLD had received previous tuberculosis treatment, which might lead to development of resistance and late diagnosis.

Keywords: Nontuberculous mycobacteria; Mycobacterium infections, nontuberculous; Lung diseases.

Objective: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. Methods: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. Results: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. Conclusions: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.

Keywords: Tuberculosis/diagnosis; Molecular diagnostic techniques; Sputum.

Objective: To identify factors predictive of mortality in patients admitted to the ICU with tuberculosis (TB)/HIV coinfection in the Manaus, Amazon Region. Methods: This was a retrospective cohort study of TB/HIV coinfected patients over 18 years of age who were admitted to an ICU in the city of Manaus, Brazil, between January of 2011 and December of 2014. Sociodemographic, clinical, and laboratory variables were assessed. To identify factors predictive of mortality, we employed a Cox proportional hazards model. Results: During the study period, 120 patients with TB/HIV coinfection were admitted to the ICU. The mean age was 37.0 ± 11.7 years. Of the 120 patients evaluated, 94 (78.3%) died and 62 (66.0%) of those deaths having occurred within the first week after admission. Data on invasive mechanical ventilation (IMV) and ARDS were available for 86 and 67 patients, respectively Of those 86, 75 (87.2%) underwent IMV, and, of those 67, 48 (71.6%) presented with ARDS. The factors found to be independently associated with mortality were IMV (p = 0.002), hypoalbuminemia (p = 0.013), and CD4 count < 200 cells/mm3 (p = 0.002). Conclusions: A high early mortality rate was observed among TB/HIV coinfected ICU patients. The factors predictive of mortality in this population were IMV, hypoalbuminemia, and severe immunosuppression.

Keywords: Mycobacterium tuberculosis; Critical care; Respiration, artificial; Acquired immunodeficiency syndrome.

Objective: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. Methods: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. Results: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. Conclusions: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement.

Keywords: Tuberculosis/diagnosis; Emergency treatment; Treatment outcome; Delivery of health care.

Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

Keywords: Tuberculosis, pulmonary/prevention & control; Mycobacterium tuberculosis; Lung diseases/etiology; Child; Adolescent.

Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions.

Keywords: Tuberculosis/epidemiology; Tuberculosis/prevention & control; Diabetes mellitus/prevention & control; Smoking/adverse effects; Alcohol drinking/adverse effects; Street drugs/adverse effects.

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.

Keywords: Tuberculosis/therapy; Tuberculosis, multidrug-resistant; Extensively drug-resistant tuberculosis; Antitubercular agents.

The objective of this systematic review was to select articles including chest X-ray or chest CT findings in patients who developed pulmonary tuberculosis following solid organ transplantation (lung, kidney, or liver). The following search terms were used: "tuberculosis"; "transplants"; "transplantation"; "mycobacterium"; and "lung". The databases used in this review were PubMed and the Brazilian Biblioteca Virtual em Saúde (Virtual Health Library). We selected articles in English, Portuguese, or Spanish, regardless of the year of publication, that met the selection criteria in their title, abstract, or body of text. Articles with no data on chest CT or chest X-ray findings were excluded, as were those not related to solid organ transplantation or pulmonary tuberculosis. We selected 29 articles involving a collective total of 219 patients. The largest samples were in studies conducted in Brazil and South Korea (78 and 35 patients, respectively). The imaging findings were subdivided into five common patterns. The imaging findings varied depending on the transplanted organ in these patients. In liver and lung transplant recipients, the most common pattern was the classic one for pulmonary tuberculosis (cavitation and "tree-in-bud" nodules), which is similar to the findings for pulmonary tuberculosis in the general population. The proportion of cases showing a miliary pattern and lymph node enlargement, which is most similar to the pattern seen in patients coinfected with tuberculosis and HIV, was highest among the kidney transplant recipients. Further studies evaluating clinical data, such as immunosuppression regimens, are needed in order to improve understanding of the distribution of these imaging patterns in this population.

Keywords: Tomography, X-ray computed; Radiography; Tuberculosis, pulmonary; Lung/transplantation; Kidney/transplantation; Liver/transplantation.