Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment / Papel do polimorfismo rs4073 do gene IL8 na toxicidade do sistema nervoso central em pacientes em tratamento para tuberculose multirresistente

ABSTRACT Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

RESUMO Objetivo: Determinar o papel do polimorfismo rs4073 do gene IL8 na previsão do risco de toxicidade do sistema nervoso central (SNC) em pacientes em tratamento farmacológico padrão para tuberculose multirresistente (TBMR). Métodos: Amostras de sangue de uma coorte de 85 pacientes com TBMR que assinaram um termo de consentimento livre e esclarecido e que estavam recebendo tratamento com medicamentos antituberculosos de segunda linha foram amplificadas para o gene IL8 (rs4073) e genotipadas. Todos os pacientes foram avaliados clinicamente quanto a evidências de toxicidade do tratamento e categorizados de acordo com os achados. Foram avaliadas as associações brutas e ajustadas. Resultados: As principais queixas enquadraram-se nas seguintes categorias: toxicidade do SNC; toxicidade gastrointestinal; toxicidade cutânea; e toxicidade ocular e ototoxicidade. Sintomas de toxicidade gastrointestinal foram relatados por 59% dos pacientes, e sintomas de toxicidade do SNC foram relatados por 42,7%. Foram identificados os seguintes genótipos de IL8 (rs4073): AA, em 64 dos participantes; AT, em 7; TT, em 11. Houve associação significativa entre o modelo dominante de herança e toxicidade do SNC no modelo bruto (p = 0,024; OR = 3,57; IC95%: 1,18-10,76) e no ajustado (p = 0,031; OR = 3,92; IC95%: 1,13-13,58). O genótipo AT+TT do gene IL8 (rs4073) apresentou risco 3,92 vezes maior de toxicidade do SNC que o genótipo AA. Conclusões: O genótipo AT+TT tende a se associar a um maior risco de características clínicas adversas durante o tratamento da TBMR.

Avances en tuberculosis en el 54° congreso chileno de enfermedades respiratorias. 1ra parte: nuevos esquemas acortados para tuberculosis drogoresistente ¿son adecuados para todos? / New shortened schemes for drug-resistant tuberculosis: are they suitable for everyone?

En esta presentación se realiza un recorrido a través de los diferentes esquemas terapéuticos de la tuberculosis drogo-resistente. Se muestra como los investigadores utilizan los nuevos fármacos disponibles y desarrollan diferentes esquemas cada vez más acortados y de administración por vía oral exclusiva, con la intención de lograr una mayor eficacia de curación de la tuberculosis resistente, con menos efectos colaterales y menor letalidad. La búsqueda de esquemas con una duración similar a las terapias de casos sensibles de tuberculosis (esquemas primarios de 6 meses) es el objetivo principal. Las pruebas moleculares como el Xpert ayudan enormemente a seleccionar los esquemas de terapia, según el perfil de susceptibilidad de los casos (resistencia a isoniazida, rifampicina, fluorquinolonas y combinaciones). Las terapias actuales de la tuberculosis drogo-resistente se basan en nuevos fármacos como fluorquinolonas, bedaquilina y linezolid, pero otros fármacos como pretomanid y delamanid también están siendo recomendados.

This presentation takes a tour through the different therapeutic schemes of drug-resistant tuberculosis. It shows how researchers use the new drugs available and develop different increasingly shortened schedules and exclusive oral administration, with the intention of achieving greater efficacy in curing resistant tuberculosis, with fewer side effects and lower lethality. The search for regimens with a duration similar to therapies of sensitive cases of tuberculosis (primary regimens of 6 months) is the main objective. Molecular tests, such as Xpert, greatly help in selecting therapy regimens, according to the susceptibility profile of the cases (resistance to isoniazid, rifampicin, fluorquinolones and combinations). Current drug-resistant tuberculosis therapies are based on new drugs such as fluorquinolones, bedaquiline and linezolid, but other drugs such as pretomanid and delamanid are also being recommended.

Hepatotoxicidad por antituberculosos en pacientes con tuberculosis multidrogorresistente / Hepatotoxicity due to antitubercular drugs in multidrug-resistant tuberculosis patients

RESUMEN Objetivo: Describir las características clínicas de la injuria hepática inducida por antituberculosos (IHIA) en pacientes con tuberculosis multirresistente (MDR-TB). Materiales y métodos: Estudio retrospectivo de pacientes hospitalizados con TB-MDR e IHIA. Se utilizó los criterios de la DILI-Expert Working Group, y el instrumento de análisis de causalidad fue el RUCAM (Roussel Uclaf Causality Assessment Method). La asociación específica de la IHIA con un antituberculoso fue por un proceso de reexposición o suspensión y recuperación. Resultados: Reportamos 7 casos de MDR-TB e IHIA; la edad media (desviación estándar) fue de 39,1 (3,3) años. La media de la IHIA apareció después de 30,4 (27,70) días de iniciar el tratamiento. Tres (43,00 %) pacientes presentaron ictericia. En cuanto al patrón, en 4 (57,00 %) fue hepatocelular y en 3 (43,00 %), colestásico. En 4 pacientes, la IHIA fue leve, y moderada en 3. En todos los casos estuvo involucrada la pirazinamida (pirazinamida sola, 4; pirazinamida y etionamida, 1; pirazinamida, rifampicina e isoniazida, 1; pirazinamida y rifampicina, 1). La estancia hospitalaria media fue de 48,10 (48,70) días. Los promedios de fosfatasa alcalina (FA), alanina aminotransferasa (ALT) y gamma-glutamiltranspeptidasa (GGT) sérica fueron 2,40 (1,10), 7,9 (7,10) y 5,60 (3,70) veces el límite superior normal (NUL), respectivamente. La bilirrubina total media fue 2,30 (2,10), rango de 0,50 a 6,40 mg/dl. Como parte del esquema de alta del paciente, se administraron quinolonas a 7 pacientes (levofloxacino, 6; ofloxacino, 1), y en un paciente se agregó ácido amoxicilina/ácido clavulánico. Conclusiones: La IHIA en pacientes con TB-MDR puede aparecer después del primer mes de tratamiento. El patrón de lesión común fue hepatocelular, y la pirazinamida fue el antimicobacteriano involucrado con mayor frecuencia.

ABSTRACT Objective: To describe the clinical characteristics of drug-induced liver injury (DILI) in multidrug-resistant tuberculosis (MDR-TB) patients. Materials and methods: A retrospective study conducted in hospitalized patients with MDR-TB and DILI. The criteria of the DILI Expert Working Group were used for the diagnosis of DILI, and the RUCAM (Roussel Uclaf Causality Assessment Method) for the causality analysis. The specific association between DILI and antitubercular drugs was established by drug rechallenge or discontinuation and recovery. Results: Seven cases of MDR-TB and DILI are described in this research. The mean age (standard deviation) was 39.10 (3.30) years. Mean DILI occurred 30.40 (27.70) days after starting the treatment. Three (43.00 %) patients presented jaundice. Regarding the type of injury, four (57.00 %) had hepatocellular injury and three (43.00 %) cholestatic injury. Four patients showed mild DILI and three moderate DILI. All the patients had taken pyrazinamide (pyrazinamide alone: four patients; pyrazinamide and ethionamide: one patient; pyrazinamide, rifampin and isoniazid: one patient; pyrazinamide and rifampicin: one patient). The mean hospital stay was 48.10 (48.70) days. The mean serum alkaline phosphatase (AP), alanine aminotransferase (ALT) and gamma-glutamyl- transpeptidase (GGT) were 2.40 (1.10), 7.90 (7.10) and 5.60 (3.70) times the upper limit of normal (ULN), respectively. The mean total bilirubin was 2.30 (2.00), with a range of 0.50 to 6.40 mg/dl. As part of the discharge plan, quinolones were given to seven patients (levofloxacin: six patients; ofloxacin: one patient) and amoxicillin/clavulanic acid was added to one patient. Conclusions: MDR-TB patients may develop DILI after the first month of treatment. Hepatocellular injury was the most common type of liver injury, and pyrazinamide was the most frequently used antimycobacterial.

Tuberculosis miliar y meningitis multidrogorresistente (MDR) en paciente pediátrico: Reporte de un caso / Complicated multidrug-resistant tuberculosis (MDR) in a pediatric patient: Case report

Objetivo: Presentar el caso de un paciente pediátrico con cuadro inicial de tuberculosis (TB) ganglionar con abandono de tratamiento en 2 ocasiones que evolucionó a la forma miliar y meningitis tuberculosa multidrogorresistente. Reporte del caso: Varón de 4 años con diagnóstico inicial de tuberculosis ganglionar, que abandonó el esquema sensible de tratamiento en dos ocasiones. Tres meses después, se evidenció compromiso bilateral sugestivo de TB miliar y durante la hospitalización desarrolló tuberculosis meníngea e hidrocefalia. Por el antecedente de abandono de tratamiento, se solicitó un estudio de sensibilidad en aspirado gástrico, identificándose como multidrogorresistente; pasando al esquema EZLfxKmEtoCs y manejo de complicaciones, consiguiendo mejoría. Conclusiones: El abandono de tratamiento es una de las principales causas de resistencia a fármacos antituberculosos y de complicaciones. Es necesario reforzar la detección temprana y tratamiento efectivo de esta infección en niños, poniéndose énfasis el seguimiento de casos para evitar abandonos de tratamiento y las complicaciones consecuentes.

Objetive:To describe a pediatric case with initial diagnosis of lymph node tuberculosis (TB) that became multidrug resistant miliar and meningeal tuberculosis (TB-MDR) due to treatment dropout twice. Case report: a 4-year-old boy with initial diagnosis of lymphnode tuberculosis who had two episodes of dropout from the sensitive scheme treatment. Three months later, there was evidence of bilateral involvement suggestive of miliary TB. During hospitalization, he developed meningeal tuberculosis and hydrocephalus. Due to the history of treatment dropout, a sensitivity of gastric aspirate study was requested, identifying it as multidrug-resistant TB. He started the EZLfxKmEtoCs treatment scheme and complications management, achieving improvement. Conclusions: Treatment dropout is one of the main causes of drug resistance in tuberculosis and its complications. It is necessary to reinforce the early detection and effective treatment of this infection in children, focusing on the follow-up of cases to avoid treatment dropout and the consequent complications.

Risk factors and interventions for surgical failure of spinal tuberculosis / 中华骨科杂志

Objective:To investigate the risk factors and interventions for surgical failure of spinal tuberculosis (STB).Methods:A total of 317 STB patients aged from 11 to 86 years with an average age of 53.5±16.7 years, who received debridement and fusion with bone grafting from January 2013 to December 2019, were retrospectively analyzed, including 206 males and 111 females. The follow-up duration was at least 1 year. During the follow-up, any one of the following 1)-3) was defined as surgical failure, namely 1) the same tubercular lesion treated by surgery more than 2 times, 2) the number of unplanned readmissions related to tubercular lesion≥1, 3) drug-resistant STB or delayed healing, recurrent lesion with cold abscess/sinus tract, combined with other bacterial infection, or loosening of internal fixation. The other cases were regarded as "curative" cases. Patients' symptoms, medication history, auxiliary examination and surgical plan were collected for univariate analysis. Further, the potential risk factors for surgical failure were analyzed by binary Logistic regression. Failed cases were treated with etiological intervention, such as puncture pumping pus or debridement or revision. The necrosis or granulation tissue was collected and further detected by tuberculosis culture, metagenomic next-generation sequencing (mNGS) and real-time fluorescent quantitative PCR (RT-qPCR).Results:There were 27 cases with surgical failure. Abscess or sinus tract formation was developed in 17 cases, which accounted for 63% (17/27). Among these patients, there were 3 cases of resistance to isoniazid or rifampicin and 2 cases of resistance to isoniazid and rifampicin (multidrug resistance, MDR). Seventeen cases were treated by anti-tuberculosis treatment, while 14 cases by puncture drainage (or puncture catheter irrigation) and 3 cases by debridement and suturing. Seven cases with wound infection or poor healing accounted for 26% (7/27). Among them, 5 kinds of pathogens were detected, none of which showed tuberculosis drug resistance. All of them were treated by anti-infection and debridement suturing, while 2 of them were treated with internal fixation removal. Three cases (11%, 3/27) with internal fixation loosening were treated by revision surgery. There was statistically significant difference between the failed group and the cured group in involved multi-/jumping segment, history of type 2 diabetes, a history of more than three basic diseases, CRP at one week after surgery, WBC at one week after surgery, time of first dose, operation duration and intraoperative blood loss ( P<0.10). Binary Logistic regression analysis showed that multi-/jumping segment ( OR= 3.513, P=0.047), CRP at one week after surgery ( OR=1.021, P=0.005), first dose time ≥20 weeks ( OR=2.895, P=0.039), blood loss ≥800 ml ( OR=5.950, P=0.001) and more than three basic diseases involved ( OR=3.671, P=0.027) were independent risk factors for surgical failure. Conclusion:Early diagnosis, especially the diagnosis of drug-resistant STB and standardized anti-tubercular treatment, should be carried out effectively. Puncture and drainage of abscess is an effective therapy to treat the cases with abscess/sinus tract formation. Some cases involved multi-/jumping segments could be with higher risk of failure after internal fixation. Thus, they should be treated individually with emphasis on the segmental stability reconstruction.

Current status of antimicrobial therapy for tuberculosis / 中国基层医药

Multidrug-resistant tuberculosis has a long treatment course and a low sputum-negative conversion rate, which have always been the treatment challenges. New drugs for multidrug-resistant tuberculosis have been constantly explored by scholars worldwide. Multiple antibacterial drugs have been found to have the therapeutic effects on multidrug-resistant tuberculosis. Treatment options that can shorten the duration of tuberculosis are also being explored. Addition of certain antibacterial drugs has been found to shorten the duration of tuberculosis. This paper reviews the effects of antibacterial drugs against tuberculosis.

Bedaquiline-containing regimens and multidrug-resistant tuberculosis: a systematic review and meta-analysis / Esquemas terapêuticos com bedaquilina e tuberculose multirresistente: revisão sistemática e meta-análise

ABSTRACT Objective: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients. Methods: This was a systematic review and meta-analysis of studies published up to March 15, 2021. The pooled treatment success rates and 95% CIs were assessed with the fixed-effect model or the random-effects model. Values of p < 0.05 were considered significant for publication bias. Results: A total of 2,679 articles were retrieved by database searching. Of those, 29 met the inclusion criteria. Of those, 25 were observational studies (including a total of 3,536 patients) and 4 were experimental studies (including a total of 440 patients). The pooled treatment success rate was 74.7% (95% CI, 69.8-79.0) in the observational studies and 86.1% (95% CI, 76.8-92.1; p = 0.00; I2 = 75%) in the experimental studies. There was no evidence of publication bias (p > 0.05). Conclusions: In patients with MDR-TB receiving bedaquiline, culture conversion and treatment success rates are high even in cases of extensive resistance.

RESUMO Objetivo: A tuberculose multirresistente (MDR-TB, do inglês multidrug-resistant tuberculosis) é uma doença infecciosa potencialmente fatal. O tratamento exige múltiplos agentes antimicrobianos usados durante longos períodos. O presente estudo buscou avaliar a taxa de sucesso de esquemas terapêuticos com bedaquilina em pacientes com MDR-TB. Métodos: Trata-se de uma revisão sistemática e meta-análise de estudos publicados até 15 de março de 2021. As taxas combinadas de sucesso do tratamento e os IC95% foram avaliados por meio do modelo de efeito fixo ou do modelo de efeitos aleatórios. Valores de p < 0,05 foram considerados significativos para viés de publicação. Resultados: Por meio de buscas eletrônicas em bancos de dados, foram recuperados 2.679 artigos. Destes, 29 preencheram os critérios de inclusão. Destes, 25 eram estudos observacionais (com um total de 3.536 pacientes) e 4 eram estudos experimentais (com um total de 440 pacientes). A taxa combinada de sucesso do tratamento foi de 74,7% (IC95%: 69,8-79,0) nos estudos observacionais e de 86,1% (IC95%: 76,8-92,1; p = 0,00; I2 = 75%) nos estudos experimentais. Não foram encontradas evidências de viés de publicação (p > 0,05). Conclusões: Em pacientes com MDR-TB tratados com bedaquilina, as taxas de conversão da cultura e sucesso do tratamento são altas mesmo em casos de resistência extensa.

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts / Sequelas pulmonares da tuberculose: comparação de coortes do Brasil, Itália e México

ABSTRACT Objective: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

RESUMO Objetivo: Avaliar a função pulmonar em uma coorte de pacientes com história de tuberculose pulmonar no Brasil, bem como avaliar o declínio da função pulmonar ao longo do tempo e compará-lo com o observado em coortes semelhantes no México e Itália. Métodos: As três coortes foram comparadas quanto à idade, tabagismo, testes de função pulmonar, teste de caminhada de seis minutos e gasometria arterial. Na coorte brasileira, os resultados dos testes de função pulmonar, do teste de caminhada de seis minutos e da gasometria arterial logo após o término do tratamento da tuberculose foram comparados com os obtidos no fim do período de acompanhamento. Resultados: As três coortes foram muito diferentes quanto aos resultados dos testes de função pulmonar. Os padrões ventilatórios mais comuns nas coortes brasileira, italiana e mexicana foram o padrão obstrutivo, o padrão misto e o padrão normal [em 58 pacientes (50,9%), em 18 pacientes (41,9%) e em 26 pacientes (44,1%), respectivamente]. Apenas 2 casos de tuberculose multirresistente foram incluídos na coorte brasileira, ao passo que na coorte mexicana foram incluídos 27 casos (45,8%). As médias da PaO2 e SaO2 foram mais baixas na coorte mexicana do que na brasileira (p < 0,0001 e p < 0,002 para PaO2 e SaO2, respectivamente). Na coorte brasileira, quase todos os parâmetros funcionais se deterioraram ao longo do tempo. Conclusões: Este estudo reforça a importância do tratamento precoce e eficaz de pacientes com tuberculose sensível, pois a tuberculose multirresistente aumenta o dano pulmonar. Quando o tratamento da tuberculose é concluído, os pacientes devem ser avaliados o quanto antes e, caso se estabeleça o diagnóstico de sequelas pulmonares da tuberculose, é preciso tratá-los e oferecer-lhes reabilitação pulmonar, pois há evidências de que ela é eficaz nesses pacientes.

Barriers faced by patients in the diagnosis of multidrug-resistant tuberculosis in Brazil

ABSTRACT OBJECTIVE To understand patients' narratives about the barriers they faced in the diagnosis and treatment of multidrug-resistant tuberculosis, and their consequences in Rio de Janeiro State, Brazil. METHODS This is a qualitative cross-sectional study with non-probabilistic sampling. A theoretical saturation criterion was considered for composing the number of interviewees. Semi-structured interviews were conducted from August to December 2019 with 31 patients undergoing treatment for multidrug-resistant tuberculosis at an outpatient referral center in Rio de Janeiro. Data were transcribed and processed with the aid of the NVIVO software. Interviews were evaluated by content analysis, and their themes, cross-referenced with participants' characterization data. RESULTS Our main findings were: a) participants show a high proportion of primary drug resistance, b) patients experience delays in the diagnosis and effective treatment of multidrug-resistant tuberculosis ; c) healthcare providers fail to value or seek the diagnosis of drug-resistant tuberculosis, thus beginning the inadequate treatment for drug-susceptible tuberculosis, d) primary health units show low report rates of active case-finding and contact monitoring, and e) patients show poor knowledge about the disease. CONCLUSIONS We need to improve referral systems, and access to the diagnosis and effective treatment of multidrug-resistant tuberculosis; conduct an active investigation of contacts; intensify the training of healthcare providers, in collaboration with medical and nursing schools, in both public and private systems; and promote campaigns to educate the population on tuberculosis signs and symptoms.

Caracterización de la tuberculosis multidrogorresistente y resistente a rifampicina en Colombia / Characterization of rifampin-resistant/multidrug-resistant tuberculosis in Colombia

RESUMEN Objetivo Caracterizar la población afectada por tuberculosis multidrogorresistente y resistente a rifampicina (TB-MDR/RR) en Colombia. Métodos Estudio transversal a partir de la información nominal de los pacientes con TB-MDR/RR tratados y reportados en Colombia desde 2009 hasta 2020, usando la totalidad de las fuentes de información oficiales. Se compararon, además, las tasas de TB-MDR/RR de diferentes grupos de riesgo con la de la población general y se evaluaron variables asociadas a la TB-MDR/RR extrapulmonar y a resistencias medicamentosas. Resultados La TB-MDR/RR ha aumentado progresivamente durante la última década y se ha concentrado en hombres (64% vs. 36%, p<0,001), edades medias (mediana: 39,5 años; RIC: 27) y zonas de mayor densidad poblacional (59% de los casos en Antioquia, Valle del Cauca y Santiago de Cali). Además, al compararlas con las poblaciones de referencia que aplicaran, se evidenciaron tasas 2, 10 y 200 veces mayores en población indígena (9,45/1 000 000 vs. 4,31/1 000 000; p=0,02), prisioneros (169/1 000 000 vs. 16,9/1 000 000; p<0,001) y habitantes de calle (21/100000 vs. 0,1/100 000; p<0,001), respectivamente. Conclusiones El aumento en los casos de TB-MDR/RR y sus grupos de riesgo deben tenerse en cuenta para la planeación de políticas, distribución de recursos y atención clínica.

ABSTRACT Objective To describe the population affected by rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) in Colombia. Methods Cross-sectional study on all the patients treated for RR/MDR-TB in Colombia between 2009 and 2020, using all the official sources of information. In addition, a comparison was made between the rates of RR/MDR-TB in some higher-risk groups and average population. Finally, the variables associated to pulmonary versus extrapulmonary RR/MDR-TB and those associated to resistance to other drugs were evaluated. Results RR/MDR-TB cases have progressively increased during the last decade. These cases were concentrated in men (64% vs. 36%, p<0.001), middle aged adults (median: 39.5 years old; IQR: 27), and in geographic regions with higher population density (59% of cases in Antioquia, Valle del Cauca and Santiago de Cali). Also, the rate of RR/MDR-TB was 2, 10 and 200 times higher in indigenous (9.45/1 000 000 vs. 4.31/1 000 000; p=0.02), prisoners (169/1 000 000 vs. 16.9/1 000 000; p<0.001), and homeless population (21/100 000 vs. 0.1/100 000; p<0.001), respectively. Conclusions The increase in RR/MDR-TB cases and their concentration in higher-risk groups must be kept in mind to make better policies, a more efficient distribution of resources, and better patient care.

Estratégias assistenciais para o controle da tuberculose drogarresistente: revisão integrativa da literatura / Care strategies for controlling drug-resistant tuberculosis: integrative literature review / Estrategias asistenciales para el control de la tuberculosis farmacoresistente: revisión integradora de la literatura

Objetivo: identificar, na literatura científica, estratégias assistenciais para o controle da tuberculose drogarresistente. Método: revisão integrativa da literatura, com análise de pesquisas relevantes sobre a questão nortedora: Quais são as evidências científicas sobre as estratégias assistenciais para o controle da tuberculose drogarresistente? Busca realizada nas bases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis, Índice Bibliográfico Espanhol em Ciências da Saúde e Banco de Dados em Enfermagem, entre janeiro e março de 2020. Foram incluídos dez artigos para discussão dos resultados que responderam à questão da pesquisa, atendendo aos critérios de inclusão e exclusão. Resultados: nos estudos publicados nos últimos cinco anos, 80% abordaram estratégias assistenciais para o controle da tuberculose drogarresistente e 20% evidenciaram falhas na assistência aos portadores da doença. Conclusão: a revisão da literatura identificou várias estratégias assistenciais para o controle da tuberculose drogarresistente, com destaque para a descentralização do diagnóstico e tratamento compartilhado, possibilitando uma atenção ampliada e integral aos pacientes.

Objective: from the scientific literature, to identify care strategies for controlling drug-resistant tuberculosis. Method: this integrative literature review examined relevant research on the research question ­ What is the scientific evidence on care strategies for controlling drug-resistant tuberculosis? ­ by searching Latin American and Caribbean Health Sciences Information, Medical Literature Analysis, Índice Bibliográfico Español en Ciencias de la Salud and Banco de Dados em Enfermagem, between January and March 2020. Ten articles were included in order to discuss findings that answered the research question, after meeting the inclusion and exclusion criteria. Results: of studies published in the past five years, 80% addressed care strategies for controlling drug-resistant tuberculosis and 20% revealed shortcomings in care for patients with the disease. Conclusion: the literature review identified several care strategies for controlling drug-resistant tuberculosis, particularly by decentralized diagnosis and shared treatment, allowing expanded, comprehensive patient care.

Objetivo: identificar, en la literatura científica, estrategias de asistencia para el control de la tuberculosis farmacorresistente. Método: se trata de una revisión integradora de la literatura, con análisis de investigaciones relevantes sobre la cuestión rectora: ¿Cuáles son las evidencias científicas sobre las estrategias de asistencia para el control de la tuberculosis farmacorresistente? La búsqueda fue realizada en las bases Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Medical Literature Analysis, Índice Bibliográfico Español en Ciencias de la Salud y Banco de Datos en Enfermería, de enero a marzo de 2020. Se incluyeron diez artículos para discutir los resultados que respondieron a la pregunta de la investigación, cumpliendo con los criterios de inclusión y exclusión. Resultados: en los estudios publicados en los últimos cinco años, el 80% abordó estrategias de atención para el control de la tuberculosis farmacorresistente y el 20% mostró fallas en la atención de los pacientes con la enfermedad. Conclusión: la revisión de la literatura identificó varias estrategias asistenciales para el control de la tuberculosis farmacorresistente, con énfasis en la descentralización del diagnóstico y tratamiento compartido, permitiendo una atención ampliada e integral a los pacientes.

Mutaciones genéticas que confieren resistencia a Isoniacida en pacientes con tuberculosis en Lima Centro, Perú 2017-2018 / Genetic mutations that confer resistance to Isoniazid in patients with Tuberculosis in Lima Centro, Perú 2017- 2018

RESUMEN Se reporta la frecuencia de mutaciones genéticas KatG e inhA que confieren resistencia a isoniacida en una muestra de 777 pacientes con resistencia a isoniacida. Se utilizó la prueba GenoType® MTBDRplus y la prueba de sensibilidad convencional por el método de agar en placa. Se encontró que 54 % presentó mutación en el gen KatG; este se asoció con resistencia a estreptomicina 76,6 % (p<0.05), rifampicina 66.7 % (p<0.05) y etionamida en un 33 % (p<0.05). La mutación en el gen inhA tuvo una frecuencia de 46 %, y se asoció con resistencia a etionamida en un 68,1 % (p<0.05), rifampicina 47,2 % (p<0,05) y estreptomicina 33 % (p<0,05). En estos pacientes, la presencia de genes que confieren resistencia a isoniazida se relacionó con resistencia a otros medicamentos antituberculosos.

ABSTRACT This a report of the frequency of KatG and inhA genetic mutations that confer resistance to isoniazid in a sample of 777 patients with resistance to isoniazid. GenoType® MTBDRplus test and conventional sensitivity tests by the agar plate method were used. It was found that 54% presented mutation in the KatG gene, associated with higher resistance to streptomycin 76.6% (p <0.05), rifampicin 66.7% (p <0.05) and ethionamide in 33% (p <0.05). inhA gene mutation has a frequency of 46% and was associated with resistance to ethionamide in 68.1% (p <0.05), rifampicin 47.2% (p <0.05) and streptomycin 33% (p <0.05). In this sample, the presences of mutations that confer resistance to isoniazid was associated with resistance to other antituberculosis drugs.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association / Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

RESUMO O diagnóstico precoce e adequado da tuberculose é um dos pilares mais importantes no controle da doença. A proposta deste consenso brasileiro é apresentar aos profissionais da área de saúde um documento com as evidências mais atuais e úteis para o diagnóstico da tuberculose. Para tanto, a Comissão de Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 membros da Sociedade com reconhecida experiência em tuberculose no Brasil. Foi realizada uma revisão não sistemática dos seguintes tópicos: diagnóstico clínico, diagnóstico bacteriológico, diagnóstico radiológico, diagnóstico histopatológico, diagnóstico da tuberculose na criança e diagnóstico da tuberculose latente.

Analysis of pyrazinamide resistance of multidrug-resistant Mycobacterium tuberculosis in Henan Province and its relationship with the mutation of drug resistance-related gene pncA / 中华传染病杂志

Objective:To evaluate the performance of the sequencing method of pncA mutations in detecting pyrazinamide (PZA)resistance in multidrug-resistant tuberculosis (MDR-TB) patients in Henan Province. Methods:Sputum samples of 152 MDR-TB patients were collected from 10 drug-resistance surveillance areas in Henan Province from January to December 2018. Questionnaire survey was conducted to collect the information, such as age, gender, treatment history and sputum culture results. The questionnaire and strain samples were sent to Henan Provincial Center for Disease Control and Prevention for further study. PZA susceptibility test was performed using the liquid medium for Mycobacterium tuberculosis. The mutations of pncA were detected by polymerase chain reaction (PCR)and sequencing, then compared with the sequence of standard strain H37Rv. The association between PZA resistant phenotype and treatment outcomes was also investigated. Chi square test and independent sample t test were used for statistical analysis. Results:Among 152 MDR-TB isolates, 105 showed phenotypically PZA resistant. The proportion of PZA resistance in the isolates with isoniazid, rifampicin, ethambutol and streptomycin resistance, pre-extensively drug-resistant and extensively drug-resistant (XDR) were 80.39%(82/102), 81.13%(43/53) and 92.59%(25/27), respectively. One hundred and two isolates had mutations in the pncA gene. Based on the results of the phenotypic drug sensitivity test, the sensitivity of pncA gene mutation detection for PZA resistance was 89.52%(95% confidence interval ( CI) 81.64%-94.39%), and the specificity was 89.36%(95% CI 76.10%-96.01%). These MDR-TB isolates harbored 100 different mutation patterns in the pncA gene, including 80 point mutations and 20 indel mutations, and 13 isolates harbored multiple mutations. Seven strains had mutation in the promoter of pncA, including -7G insertion, -11T to C and -12A to G. The relative expression levels of pncA mRNA in the three groups were 0.21±0.05, 0.31±0.08 and 0.33±0.03, respectively, which were all lower than that of H37Rv(1.00). The differences were statistically significant ( t=4.57, 2.43 and 3.65, respectively, all P<0.05). The difference of the sputum negative conversion rates between patients with PZA-resistant isolates and those with PZA susceptible isolates was statistically significant at different time periods after treatment ( χ2=10.01, P=0.02). The negative conversion rate of PZA-resistant patients at the end of six months of treatment was 1.08%(1/93), and that of PZA-sensitive patients was 7.14%(3/42). Conclusions:The PZA resistance in MDR-TB isolates is associated with pncA mutations, which are scatered and diversified. The sputum negative conversion time of PZA-resistant patients is prolonged.

A nomogram for predicting the risk of multidrug-resistant tuberculosis / 中华传染病杂志

Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.

Prevalência de tuberculose drogarresistente e fatores associados / Prevalence of drug-resistant tuberculosis and associated factors

RESUMO Objetivo estimar a prevalência de tuberculose drogarresistente e os fatores a ela associados. Métodos estudo retrospectivo que avaliou 74.006 casos de tuberculose registrados no Sistema de Informação de Agravos de Notificação. Na análise multivariada, utilizou-se da variável desfecho "resistência medicamentosa" para estimar a razão de prevalência dos fatores associados à drogarresistência. Resultados estimou-se taxa de 0,5% de drogarresistência (n=388). Observou-se maior prevalência nos casos classificados como recidiva, reingresso pós-abandono e transferência. Houve aumento de 53,0% quando a baciloscopia de escarro foi positiva e de 6,5 vezes para cultura de escarro positiva. Efeito contrário foi observado mediante a não realização do exame diagnóstico para vírus da imunodeficiência humana. Conclusão estimou-se baixa prevalência de tuberculose drogarresistente comparada a cenários internacionais. Os principais fatores associados à doença estiveram ligados aos retratamentos e ao resultado positivo da baciloscopia e cultura de escarro.

ABSTRACT Objective to estimate the prevalence of drug-resistant tuberculosis and associated factors. Methods a retrospective study that evaluated 74,006 cases of tuberculosis registered in the Notifiable Diseases Information System. In the multivariate analysis, the outcome variable "drug resistance" was used to estimate the prevalence ratio of factors associated with drug resistance. Results a rate of 0.5% of drug resistance was estimated (n=388). A higher prevalence was observed in cases classified as relapse, post-dropout re-entry, and transfer. There was a 53.0% increase when sputum smear microscopy was positive and a 6.5 increase for positive sputum culture. The opposite effect was observed when the diagnostic test for human immunodeficiency virus was not performed. Conclusion a low prevalence of drug-resistant tuberculosis was estimated compared to international scenarios. The main factors associated with the disease were related to retreatments and positive sputum smear and culture results.

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis / Los resultados adversos en el tratamiento de la tuberculosis resistente a múltiples fármacos sobrepasan la relación fármaco-microorganismo: resultados de un análisis de correspondencia múltiple

Abstract . Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities. Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia. Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease. Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Resumen . Introducción. El tratamiento de la tuberculosis multirresistente tiene una efectividad del 50 %, afectado por múltiples factores como la sensibilidad del microorganismo, las reacciones secundarias, los factores sociales y las comorbilidades existentes. Objetivos. Describir la demografía, las características clínicas y los factores pronósticos asociados con los resultados del tratamiento en pacientes multirresistentes (TB-MDR) de Medellín, Colombia. Métodos. Se hizo un análisis retrospectivo de los datos de los pacientes con TB-MDR atendidos en el Hospital La María de Medellín, Colombia, que fueron tratados entre el 2010 y el 2015. Los pacientes se categorizaron con tratamiento exitoso (curados) o con tratamiento fallido (falla en el tratamiento, pérdida durante el seguimiento y muerte). Se determinó la asociación entre las características demográficas y clínicas, los resultados de los exámenes de laboratorio, los desenlaces del tratamiento y la información del seguimiento, utilizando análisis univariado, multivariado y de correspondencia múltiple. Resultados. De 128 pacientes con TB-MDR, 77 (60 %) tuvieron un tratamiento exitoso. De los que tuvieron un tratamiento fallido, 26 pacientes se perdieron en el seguimiento, 15 murieron y 10 tuvieron falla en el tratamiento. El tratamiento irregular, las comorbilidades y los cultivos positivos más allá de 2 meses de tratamiento se asociaron significativamente con los tratamientos fallidos (p<0,05). El análisis de correspondencia múltiple agrupó los pacientes con pérdida en el seguimiento, con HIV y tratamientos irregulares, y los pacientes con tratamientos irregulares y enfermedad pulmonar obstructiva crónica con falla en el tratamiento y muerte. Conclusión. El reconocimiento temprano de los factores que afectan el desenlace del tratamiento de los pacientes con TB-MDR es esencial; la identificación de dichos factores debería incrementar el éxito del tratamiento y contribuir al adecuado control de la TB-MDR.

Distribución geográfica y factores de riesgo de tuberculosis multidrogorresistente en el centro de Perú / Geographical distribution and risk factors for multidrug-resistant tuberculosis in central Peru

Resumen Introducción. De acuerdo con la Organización Mundial de la Salud, la tuberculosis multidrogorresistente (TB-MDR), definida como aquella en la que hay resistencia a isoniacida y rifampicina, representa una seria amenaza para la salud pública, ya que en 2018 se reportaron cerca de medio millón de nuevos casos de tuberculosis resistente a la rifampicina, de los cuales el 78% tenían TB-MDR. En Perú, 6 personas se enferman de tuberculosis (TB) cada hora y de los 27 000 casos notificados de enfermedad activa por año, el 10% corresponde a TB-MDR. Objetivo. Determinar la distribución geográfica de la TB-MDR y los factores de riesgo de esta enfermedad en la región de Junín, ubicada en el centro de Perú. Materiales y métodos. Estudio longitudinal retrospectivo de casos y controles que incluyó 3 602 personas con diagnóstico de tuberculosis confirmado con cultivo positivo para Mycobacterium tuberculosis entre enero y diciembre de 2016. Los casos fueron los pacientes con diagnóstico de TB-MDR y los controles, los demás pacientes. Resultados. Se encontró una mayor prevalencia de casos de TB-MDR en la selva central de Perú, zona con alta incidencia de TB. Al realizar el análisis multivariado, se encontraron los siguientes factores de riesgo de multidrogorresistencia: antecedente de tratamiento de la TB (OR: 1.61, IC95%: 1.14-3.26), fracaso del tratamiento previo (OR: 5.84, IC95%: 4.03-8.21) y contacto intradomiciliario con personas con TB-MDR (OR: 91.57, IC95%: 34.56-289.14). Conclusiones. La distribución geográfica de la TB-MDR es de tipo no heterogéneo con alta incidencia en la selva central. En pacientes con diagnóstico reciente de TB, se debe considerar la posibilidad de TB-MDR si presentan alguno de los factores de riesgo identificados aquí y proceden de alguna zona de alta prevalencia de esta enfermedad.

Abstract Introduction: According to the World Health Organization, multidrugresistant tuberculosis (MDR TB), defined as TB cases in which there is resistance to rifampicin and isoniazid, is a serios threat for public health, since nearly half million new cases of rinfampicin-resistant TB were reported in 2018, of which 78% were MDR TB. In Peru, 6 people fall ill with tuberculosis (TB) every hour and out of the 27 000 active TB cases reported per year, 10% are MDR TB cases. Objective: To determine the geographical distribution of MDR TB and the risk factors of this disease in the Junín region, located in central Peru. Materials and methods: Retrospective longitudinal case-control study. The study population consisted of 3 602 people with TB diagnosis confirmed with positive cultures for M. tuberculosis between January and December 2016. Cases were made up of patients diagnosed with MDR TB, and the remaining patients were the controls. Results: A higher prevalence of MDR-TB cases was observed in the central jungle of Peru, an area with a high incidence of TB. After performing the multivariate analysis, the following risks factors for developing multidrug resistance were found: history of TB treatment (OR: 1.61, 95%CI: 1.14-3.26), prior treatment failure (OR: 5.84, 95%CI: 4.03-8.21) and intra-household contact with people with MDR-TB (OR: 91.57, 95%CI: 34.56-289.14). Conclusions: The geographical distribution of MDR TB is non-heterogeneous and has a high incidence in the central jungle. In the case of patients recently diagnosed with TB, the possibility of MDR TB diagnosis should be considered if they have at least one of the risk factors identified here and come from an area where this disease is highly prevalent.

Analysis of anti-tuberculosis drug resistance and sociodemographic and clinical aspects of patients admitted in a referral hospital / Análise da resistência a medicamentos antituberculose e aspectos sociodemográficos e clínicos de pacientes atendidos em hospital referência

ABSTRACT Objective To determine the occurrence of anti-tuberculosis drug resistance and its association with sociodemographic and clinical characteristics of patients in a referral hospital. Methods This was a cross-sectional study based on data from patients who had mycobacterial culture identified and defined antimicrobials sensitivity profile (June 2014 to February 2016). The descriptive statistical analysis and Fisher's exact test were used to compare proportions. Results The study included 104 patients who had positive results for Mycobacterium tuberculosis . Bacilloscopy had high positivity (93.3%). A total of 15 patients (14.4%) had resistant strains and six (5.6%) multidrug-resistant. The sociodemographic and clinical characteristics were not related with resistance. Conclusion This study contributed to further the understandings about the tuberculosis patients' profile, the study also served as a tool for development of specific public policies. Patients diagnosed with resistant tuberculosis must be under greater supervision.

RESUMO Objetivo Verificar a ocorrência de resistência a fármacos antituberculose e a associação com características sociodemográficas e clínicas de pacientes de um hospital referência. Métodos Estudo transversal, com dados de pacientes que tiveram a cultura de micobactérias identificada e o respectivo perfil de sensibilidade aos antimicrobianos definido (junho de 2014 a fevereiro de 2016). Foram realizados a análise estatística descritiva e o teste exato de Fisher, para comparação de proporções. Resultados O estudo envolveu 104 pacientes, e todos tiveram resultados para Mycobacterium tuberculosis . A baciloscopia atingiu alta positividade (93,3%), e 15 pacientes (14,4%) apresentaram linhagens resistentes, sendo 6 (5,6%) multirresistentes. As características sociodemográficas e clínicas não foram associadas à resistência. Conclusão A pesquisa permitiu conhecer melhor o perfil dos pacientes com tuberculose e constitui ferramenta para elaboração de políticas públicas específicas. Os pacientes diagnosticados com tuberculose resistente devem ser submetidos à maior supervisão.

Management of multidrug-resistant tuberculosis: main recommendations of the Brazilian guidelines / Manejo da tuberculose multirresistente: elementos centrais das recomendações brasileiras

ABSTRACT Over the years, various recommendations have been made in pursuit of controlling resistance to antituberculosis drugs, especially multidrug resistance, in Brazil. Given the importance of standardizing those recommendations, the aim of this study was to describe the main recommendations of the Brazilian guidelines, primarily those related to the treatment and follow-up of cases of tuberculosis. From August through October of 2018, a document search was conducted via the websites of the Brazilian National Ministry of Health, the Brazilian National Tuberculosis Control Program, the JBP, and the Official Gazette of the Federal Republic of Brazil. Data were collected systematically by using a protocol designed specifically for this study. Documents published between 2004 and 2018 were selected. It was possible to understand and trace the history of the measures for the control of multidrug-resistant tuberculosis in Brazil from 2004, when the first documents related to the disease were published, up to 2018, when the second edition of the Brazilian National Guidelines for the Control of Tuberculosis was published. The contents of the documents were analyzed and grouped by case definition, diagnostic criteria, treatment, use of directly observed treatment; mechanisms of social protection for patients; data tools; and organization of care. This analysis allowed us to understand the efforts towards standardizing some measures in Brazil, not only identifying advances in the alignment with international prerogatives (case definition, incorporation of diagnostic technology, and treatment regimens) but also underscoring the need for greater clarity regarding the mechanisms of social protection and the organization of the care provided via the Brazilian health care system.

RESUMO No Brasil, algumas recomendações têm sido feitas ao longo dos anos em busca de controlar a resistência às drogas antituberculose, em especial a multirresistência. Tendo em vista a importância dessa normatização, o objetivo do presente estudo foi descrever os elementos centrais dos documentos nacionais, especialmente em relação ao tratamento e acompanhamento dos casos. Entre agosto e outubro de 2018, foi realizada uma pesquisa documental, com busca eletrônica nos sites do Ministério da Saúde, Programa Nacional de Controle da Tuberculose, JBP e Diário Oficial da União. A coleta de dados ocorreu de forma sistematizada com roteiro construído para esta pesquisa. Os documentos foram publicados entre 2004 e 2018. Foi possível entender e traçar o histórico das medidas de controle da tuberculose multirresistente no Brasil a partir de 2004, com as primeiras publicações referentes à doença, até 2018, quando ocorreu a publicação da segunda edição do Manual de Recomendações para o Controle da Tuberculose no Brasil. Os conteúdos dos documentos foram analisados e agrupados quanto a definição de caso, critérios diagnósticos, tratamento, condução do tratamento diretamente observado, mecanismos de proteção social aos doentes, ferramentas de informação e organização da assistência. Tal análise permitiu compreender os esforços no sentido da padronização de algumas condutas no território nacional, identificando avanços quanto ao alinhamento com as prerrogativas internacionais (definição de caso, incorporação de tecnologia diagnóstica e esquemas de tratamento); porém, evidenciou-se a necessidade de maior clareza quanto aos mecanismos de proteção social e à organização da assistência no sistema de saúde nacional.