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      Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation Translated title: Tratamento da tuberculose grave e suas sequelas: da terapia intensiva à cirurgia e reabilitação

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          ABSTRACT

          Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

          RESUMO

          A tuberculose multirresistente e a tuberculose extensivamente resistente ainda são um desafio para médicos e especialistas em saúde pública. Os desfechos globais do tratamento ainda são insatisfatórios; apenas 54% dos pacientes têm um desfecho positivo. Os desfechos globais são ainda piores em pacientes infectados por cepas altamente resistentes. O tratamento da tuberculose multirresistente/extensivamente resistente é difícil em virtude dos eventos adversos frequentes, da longa duração dos esquemas terapêuticos, do alto custo dos medicamentos de segunda linha, das sequelas pós-infecciosas crônicas e da perda da função orgânica. Esforços de pesquisa (estudos e ensaios) estão em andamento e têm diversos objetivos: aumentar as taxas de sucesso do tratamento; compreender o potencial de medicamentos novos e reaproveitados; encurtar o tratamento e reduzir as taxas de eventos adversos. Espera-se que melhor acesso ao diagnóstico rápido, maior conhecimento e terapias mais eficazes reduzam as complicações e o comprometimento da função pulmonar. O objetivo deste artigo é discutir o tratamento da tuberculose grave (potencialmente fatal, que necessita de níveis maiores de atenção) e suas sequelas, desde a terapia intensiva até o pós-operatório, reabilitação e recuperação. São também discutidas as intervenções não farmacológicas disponíveis para tratar sequelas crônicas e melhorar a qualidade de vida dos pacientes. Como a maioria dos casos de tuberculose multirresistente/extensivamente resistente resulta em comprometimento da função pulmonar (obstrução principalmente, mas às vezes restrição), qualidade de vida prejudicada e desempenho reduzido (medido por meio de testes de caminhada ou outros), são necessárias outras intervenções (cessação do tabagismo, reabilitação pulmonar, vacinação e prevenção de infecções bacterianas secundárias/exacerbações, por exemplo, complementadas por apoio psicológico e nutricional).

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          Most cited references53

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          Tuberculosis.

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            Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study.

            Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.
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              Pulmonary impairment after tuberculosis.

              Pulmonary impairment subsequent to a cure of pulmonary tuberculosis has been described only in selected populations. We compared pulmonary function in a case-control study of 107 prospectively identified patients with pulmonary tuberculosis who had completed at least 20 weeks of therapy and 210 patients with latent tuberculosis infection (LTBI). Both groups had similar risk factors for pulmonary impairment. Impairment was present in 59% of tuberculosis subjects and 20% of LTBI control subjects. FVC, FEV1, FEV1/FVC ratio, and the midexpiratory phase of forced expiratory flow were significantly lower in the treated pulmonary tuberculosis patients than in the comparison group. Ten patients with a history of pulmonary tuberculosis (9.4%) had less than half of their expected vital capacity vs one patient (0.53%) in the LTBI group. Another 42 patients (39%) with tuberculosis had between 20% and 50% of the expected vital capacity vs 36 patients with LTBI (17%). After adjusting for risk, survivors of tuberculosis were 5.4 times more likely to have abnormal pulmonary function test results than were LTBI patients (p > 0.001; 95% confidence interval, 2.98 to 9.68). Birth in the United States (odds ratio [OR], 2.64; p = 0.003) and age (OR, 1.03; p = 0.005) increased the odds of impairment. Pulmonary impairment was more common in cigarette smokers; however, after adjusting for demographic and other risk factors, the difference did not reach statistical significance (p = 0.074). These findings indicate that pulmonary impairment after tuberculosis is associated with disability worldwide and support more aggressive case prevention strategies and posttreatment evaluation. For many persons with tuberculosis, a microbiological cure is the beginning not the end of their illness.
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                Author and article information

                Journal
                J Bras Pneumol
                J Bras Pneumol
                jbpneu
                Jornal Brasileiro de Pneumologia
                Sociedade Brasileira de Pneumologia e Tisiologia
                1806-3713
                1806-3756
                Mar-Apr 2019
                Mar-Apr 2019
                : 45
                : 2
                : e20180324
                Affiliations
                [1 ]. Barts Health NHS Trust, Royal London Hospital, Division of Infection, London, United Kingdom.
                [2 ]. Blizard Institute, Barts and the London School of Medicine and Dentistry, Centre for Primary Care and Public Health, London, United Kingdom.
                [3 ]. Clínica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, DF, México.
                [4 ]. Istituti Clinici Scientifici Maugeri - IRCCS - Tradate, Italia.
                [5 ]. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre (RS) Brasil.
                Author notes
                [Correspondence to: ] Giovanni Battista Migliori. Istituti Clinici Scientifici Maugeri IRCCS, Via Roncaccio 16, 21049, Tradate, Italia. Tel.: 39 0331 829404. E-mail: giovannibattista.migliori@ 123456icsmaugeri
                Author information
                http://orcid.org/0000-0001-9424-6551
                http://orcid.org/0000-0002-8453-3634
                http://orcid.org/0000-0002-1918-9726
                http://orcid.org/0000-0002-3982-642X
                http://orcid.org/0000-0003-2298-1623
                http://orcid.org/0000-0003-0230-2734
                http://orcid.org/0000-0002-0380-1116
                http://orcid.org/0000-0002-2597-574X
                Article
                00500
                10.1590/1806-3713/e20180324
                6733754
                31038649
                121a0b34-ee94-4eb8-81e8-166703e0a9cc
                © 2019 Sociedade Brasileira de Pneumologia e Tisiologia

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 16 October 2018
                : 12 January 2019
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 69
                Categories
                Review Article

                extensively drug-resistant tuberculosis,tuberculosis, multidrug-resistant,critical care,smoking cessation,tuberculose extensivamente resistente a medicamentos,tuberculose resistente a múltiplos medicamentos,cuidados críticos,abandono do hábito de fumar

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