Diagnóstico de tuberculosis en pediatría / Diagnosis of tuberculosis in pediatrics

La tuberculosis sigue siendo una epidemia mundial y en Chile no ha mostrado una tendencia descendente en los últimos años, con un aumento en los casos infantiles. En los niños, el diagnóstico es un reto debido a la baja carga bacilar y las características de las lesiones, que suelen ser cerradas. Métodos tradicionales como los cultivos, considerados anteriormente como el gold standard, con frecuencia arrojan resultados negativos. Sin embargo, los avances en pruebas moleculares han permitido un progreso significativo en la confirmación bacteriológica. Otras herramientas diagnósticas, como la prueba de tuberculina (PPD) y los ensayos de liberación de interferón gamma (IGRAs), tienen sensibilidades y especificidades variables, siendo útiles como pruebas complementarias. Las imágenes juegan un papel clave en la evaluación diagnóstica de tuberculosis pulmonar y extrapulmonar en pacientes pediátricos. Esta revisión aborda la epidemiología y el proceso diagnóstico de la tuberculosis infantil.

Tuberculosis remains a global epidemic, and in Chile, it has not shown a downward trend in recent years, with an increase in pediatric cases. Diagnosing tuberculosis in children presents challenges due to the low bacillary load and the closed nature of the lesions. Traditional methods like cultures, once considered the gold standard, often yield negative results. However, advances in molecular testing have significantly improved bacteriological confirmation. Other diagnostic tools, such as the tuberculin skin test (PPD) and interferon-gamma release assays (IGRAs), offer variable sensitivities and specificities and are useful as complementary tests. Imaging plays a critical role in the diagnostic evaluation of pulmonary and extrapulmonary tuberculosis in pediatric patients. This review addresses the epidemiology and diagnostic process of pediatric tuberculosis.

Admissions by tuberculosis in a regional reference Center. A complex and worrying scenario / Ingresos por tuberculosis en un hospital regional. Un escenario complejo y preocupante

OBJECTIVES: To characterize clinical aspects, evaluate the diagnostic opportunity, and identify factors associated with mortality in patients hospitalized for tuberculosis (TB). METHODS: Retrospective study of patients admitted for TB to a Regional Hospital in Chile between 2011 and 2019. RESULTS: 142 TB events required hospitalization in this period (38.2% of total cases). All risk groups were identified, with a significant increase in patients with diabetes mellitus. The pulmonary location was the most frequent (71.1%), followed by disseminated forms (16.2%). The sensitivity of microscopy smear in cases of pulmonary TB (isolated or combined) was 78.8% and lower in cases of bronchoalveolar lavage (58.3%). PCR was only occasionally applied (< 10%) with a sensitivity of 100% in sputum samples. Its use increased progressively and reached a positivity of 33% (6 out of 18 cases) in cases with negative sputum staining. The median time between symptom onset and diagnosis was prolonged (9 weeks), and 32.5% of all regional events were diagnosed at the hospital. Dose adjustments (22.1%), corticosteroid use (25%), and treatment interruptions were frequent (11%). Lethality reached 19%, and by multivariate analysis, only shock was associated with a fatal outcome. CONCLUSIONS: In this case series, the diagnosis of TB cases was delayed, scarcely diagnosed by molecular methods, highly concentrated at the hospital level, required admission in a large percentage of cases, and had a high case-fatality rate.

OBJETIVOS: Caracterizar aspectos clínicos, evaluar la oportunidad diagnóstica e identificar factores asociados a mortalidad en pacientes ingresados por tuberculosis (TB). MÉTODOS: Estudio retrospectivo de pacientes ingresados por TB a un Hospital Regional en Chile entre el 2011 y 2019. RESULTADOS: Un total de 142 eventos de TB requirieron hospitalización en el período (38,2% del total). Todos los grupos de riesgo fueron identificados con un aumento significativo de los pacientes con diabetes mellitus. La localización pulmonar fue la más frecuente (71,1%), seguida de la forma diseminada (2 o más sitios; 16,2%). La sensibilidad de la tinción de expectoración en casos de TB pulmonar (aislada o combinada) fue de 78,8% y más baja en casos de lavado broncoalveolar (58,3%). La PCR fue sólo ocasionalmente aplicada (< 10%) con una sensibilidad del 100% en muestras de expectoración. Su uso aumentó progresivamente en el período y el incremento diagnóstico de TB en casos con tinción negativa de expectoración estudiados con PCR fue de 33% (6 de 18 casos). La mediana entre inicio de síntomas y el diagnóstico fue prolongada (9 semanas) y el 32,5% de los eventos regionales fueron diagnosticados en el hospital. Los ajustes de dosis (22,1%), uso de corticoides (25%) e interrupciones del tratamiento fueron hechos frecuentes (11%). La letalidad alcanzó 19% y en el análisis multivariado sólo la aparición de shock se asoció a un desenlace fatal. CONCLUSIONES: En esta serie de casos, el diagnóstico de casos de TB fue tardío, infrecuentemente diagnosticado por métodos moleculares, concentrado en la atención terciaria, requirió hospitalización en un gran porcentaje de casos y tuvo una elevada letalidad.

Caracterización clínica y microbiológica de pacientes con trazas en Xpert MTB/RIF Ultra / Clinical and microbiological characterization of patients with Xpert MTB/RIF Ultra traces

INTRODUCCIÓN: El Xpert MTB/RIF Ultra (Ultra) ha mejorado dramáticamente el diagnóstico de la tuberculosis (TBC). Con él ha nacido la categoría de trazas, que es la menor carga bacilar detectable por este examen. OBJETIVO: Describir las características clínicas de los pacientes con presencia de trazas en el Ultra y evaluar la confirmación de la TBC como diagnóstico clínico. MATERIALES Y MÉTODOS: Estudio descriptivo de serie de casos. Se extrajo la información de fichas clínicas de pacientes con positividad a trazas. Se confrontaron datos clínicos, microbiológicos e histopatológicos. RESULTADOS: Se analizaron 21 pacientes. La edad promedio fue de 52 años. Todos los casos presentaron baciloscopias negativas. Cuatro cultivos en medio líquido MGIT fueron positivos, dos en pleura parietal, uno en líquido pleural y otro en expectoración. En pleura parietal, tres casos presentaron granulomas con necrosis caseosa y un granuloma esbozos de necrosis. En tejido pulmonar se observaron dos casos con granulomas con esbozos de necrosis y dos con granulomas no necrotizantes. Tres pacientes tenían el antecedente de TBC previa, se interpretó la positividad de trazas en ellos como falsos positivos. Finalmente se diagnosticaron 13 casos como TBC activa, donde cinco de ellos fueron TBC pleurales. La mayor concordancia clínica, microbiológica e histopatológica fue en muestras de líquido y tejido pleural. DISCUSIÓN: Se debe interpretar con cautela los hallazgos de esta prueba en muestras de vía aérea; el análisis multidisciplinario (clínica, imágenes, microbiología, histología) es crucial en las decisiones de nuestras conductas clínicas futuras. El hallazgo de trazas en pleura tiene, a nuestro parecer, un alto valor diagnóstico en el estudio de la tuberculosis en esta localización.

INTRODUCTION: Xpert MTB/RIF Ultra has dramatically changed the diagnosis of tuberculosis. A new category called traces appeared, which is the smallest amount of bacillar load detectable. OBJECTIVE: Describe the clinical characteristics of patients that present traces in Xpert MTB/RIF Ultra test, and to evaluate the confirmation of tuberculosis as clinical diagnosis. METHODS: We perform a descriptive case series study. Information was recovered from clinical records of patients with positive test for traces. Clinical, histopathological and microbiological results were confronted. RESULTS: Twenty one patients were analyzed. The mean age was 52 years-old. All cases had negative smear microscopy and four MGIT cultures were positive, two in pleural fluid and another in sputum. In parietal pleura, three cases presented granulomas with caseous necrosis, and one showed granuloma with very little necrosis. In pleural tissue we observed two cases of granulomas with traces of necrosis and two with non-necrotizing granulomas. Three patients had history of previous tuberculosis and positive traces, the test was interpreted as a false positive result. Finally, active tuberculosis was diagnosed in 13 cases, and five of them were pleural tuberculosis. The highest clinical, microbiological and histopathological agreement was in fluid and pleural tissue samples. DISCUSSION: The findings of Xpert MTB/RIF Ultra in airway samples must be interpreted carefully. Multi-disciplinary analysis is crucial in future clinical decisions. The finding of traces in pleura has, in our opinion, a high diagnostic value in the study of tuberculosis in this location.

Tuberculose pulmonar causada pelo uso de infliximab em paciente com Doença de Crohn / Pulmonary tuberculosis caused by the use of infliximab in a patient with Crohn's Disease

A doença de Crohn é uma patologia caracterizada pela inflamação transmural do trato gastrointestinal, compondo o espectro das doenças inflamatórias intestinais. Nos casos mais graves, dispõe de tratamento com uso de agentes biológicos e imunomoduladores que podem à reativação ou exacerbação de doenças infecciosas preexistentes. Este relato de caso trata de uma paciente do sexo feminino de 24 anos, diagnosticada com Doença de Crohn há 10 anos, evoluindo com necessidade de tratamento com infliximab e, após período de menos de 1 ano, apresentou odinofagia progressiva, dor abdominal e diarreia, além de perda ponderal, sudorese noturna e febre diária. Tomografia computadorizada de tórax evidenciou árvore em brotamento, sendo confirmado diagnóstico de tuberculose pulmonar pelo Teste Rápido Molecular no escarro e provável tuberculose laríngea e intestinal.

Crohn's disease is a pathology characterized by transmural inflammation of the gastrointestinal tract, comprising the spectrum of Inflammatory Bowel Diseases. In the most severe cases, treatment using biological agents and immunomodulators may be available, which can lead to the reactivation or exacerbation of preexisting infectious diseases. This case report is about a 24-year-old female patient, diagnosed with Crohn's disease 10 years ago, evolving in need of treatment with Infliximab and, after a period of less than 1 year, she presented progressive odynophagia, abdominal pain and diarrhea, in addition to weight loss, night sweats and daily fever. Chest computer tomography showed a tree in bud, and the diagnosis of pulmonary tuberculosis was confirmed by the Rapid Molecular Test in the sputum and probable laryngeal and intestinal tuberculosis.

Tuberculosis miliar / Miliary tuberculosis

Introducción: La tuberculosis es considerada como la enfermedad infecciosa más importante del mundo, a pesar de los esfuerzos que se han invertido para su control. Es producida por el complejo mycobacterium tuberculosis. El órgano más afectado es el pulmón, aunque puede tener repercusión extrapulmonar. Objetivo: Presentar el caso de un paciente diagnosticado de tuberculosis miliar a través del esputo posbroncoscopia. Caso clínico: Se expone el caso de un paciente diagnosticado de una tuberculosis miliar al cual se le realizó broncoscopia diagnóstica y lavado bronquial para bacilo ácido alcohol resistente (BAAR), el cual fue negativo. El diagnóstico se obtuvo por esputo BAAR posbroncoscopia. Conclusiones: El esputo posbroncoscopia es una opción con adecuada rentabilidad en el diagnóstico de esta enfermedad infecciosa(AU)

Introduction: Tuberculosis is considered the most important infectious disease in the world, despite the efforts that have been invested to control it. It is produced by the mycobacterium tuberculosis complex. The most affected organs are the lungs, although it can have extrapulmonary repercussions. Objective: To report the case of a patient diagnosed with miliary tuberculosis through post-bronchoscopy sputum. Clinical case report: The case of a patient diagnosed with miliary tuberculosis is reported. This patient underwent diagnostic bronchoscopy and bronchial lavage for acid-alcohol-resistant bacillus (ABB), which was negative. The diagnosis was obtained by postbronchoscopy ARB sputum. Conclusions: Post-bronchoscopy sputum is an option, with adequate profitability in the diagnosis of this infectious disease(AU)

Estrategia de pesquisa sistemática y seguimiento prolongado revela alto número de nuevas infecciones tuberculosas en contactos adultos en la Región Metropolitana, Chile / Systematic screening of adult household contacts of patients with active pulmonary tuberculosis reveals high rates of new infections during follow-up

Background: Contact investigation is cardinal in the control of tuberculosis (TB) since it helps to stop its transmission. In Chile, the National TB Program strategy does not include latent TB infection testing, regular chemoprophylaxis or follow-up in adults. Active TB was found in only 1.2% of contacts at country-level during 2018. Aim: To evaluate the performance of a systematic screening of adult household contacts with targeted chemoprophylaxis and prolonged active follow-up. Material and Methods: Prospective cohort of household contacts in Santiago. Two face-to-face visits (at 0 and 12 weeks) that included QuantiFERON TB-Gold plus tests (QFT), chest radiography (CXR) at 0 and 24 weeks and, periodic text messaging or phone call follow-up for up to 48 weeks were implemented. Contacts with positive QFT were referred for TB chemoprophylaxis. Results: A total of 200 contacts were enrolled, 69% were migrants. At baseline evaluation, 45% had a positive QFT result and 1.6% had co-prevalent active TB. At follow-up, 13% contacts further converted to QFT (+), and 5.1% more were diagnosed with active TB (mean follow-up time 32 weeks). Of these 10 further active TB cases, 6 (60%) had a negative QFT and all (100%) had normal CXR at baseline; while three cases occurred in QFT converters. Conclusions: In this cohort of household contacts, 6.7 % were diagnosed with active TB (more than 2/3 at follow-up) and 13% had a late QFT (+) conversion. Active and prolonged contacts' follow-up are essential to detect new infections and tackle the TB epidemic in Chile.

Association between the radiological presentation and elapsed time for the diagnosis of pulmonary tuberculosis in the emergency department of a university hospital / Associação entre apresentação radiológica e tempo decorrido para o diagnóstico da tuberculose pulmonar no serviço de emergência de um hospital universitário

ABSTRACT Objective: To evaluate the radiological presentation of patients with pulmonary tuberculosis diagnosed in the emergency department and to investigate its association with the time to diagnosis. Methods: This was a prospective observational study involving patients diagnosed with pulmonary tuberculosis in the emergency department of a tertiary university hospital in southern Brazil. Chest X-rays taken on admission were evaluated by a radiologist. The various patterns of radiological findings and locations of the lesions were described. The main study outcome was the total time elapsed between the initial radiological examination and the diagnosis of tuberculosis. Results: A total of 78 patients were included in the study. The median time from chest X-ray to diagnosis was 2 days, early and delayed diagnosis being defined as a time to diagnosis < 2 days and ≥ 2 days, respectively. Sputum smear positivity was associated with early diagnosis (p = 0.005), and positive culture was associated with delayed diagnosis (p = 0.005). Early diagnosis was associated with the presence of sputum (p = 0.03), weight loss (p = 0.047), cavitation (p = 0.001), and consolidation (p = 0.003). Pulmonary cavitation was found to be an independent predictor of early diagnosis (OR = 3.50; p = 0.028). Conclusions: There is a need for tuberculosis-specific protocols in emergency departments, not only to avoid delays in diagnosis and treatment but also to modify the transmission dynamics of the disease.

RESUMO Objetivo: Avaliar a apresentação radiológica de pacientes com tuberculose pulmonar diagnosticada no serviço de emergência e investigar sua associação com o tempo para o diagnóstico. Métodos: Estudo observacional prospectivo envolvendo pacientes diagnosticados com tuberculose pulmonar no serviço de emergência de um hospital universitário terciário no sul do Brasil. As radiografias de tórax realizadas na admissão foram avaliadas por um radiologista. Foram descritos os diferentes padrões de achados radiológicos e as localizações das lesões. O desfecho principal do estudo foi o tempo total decorrido entre o exame radiológico inicial e o diagnóstico de tuberculose. Resultados: Um total de 78 pacientes foi incluído no estudo. A mediana de tempo entre a radiografia de tórax e o diagnóstico foi de 2 dias, sendo os diagnósticos precoce e tardio definidos como tempo para o diagnóstico < 2 dias e ≥ 2 dias, respectivamente. A positividade da baciloscopia de escarro associou-se ao diagnóstico precoce (p = 0,005), e a cultura positiva associou-se ao diagnóstico tardio (p = 0,005). O diagnóstico precoce associou-se à presença de escarro (p = 0,03), perda de peso (p = 0,047), cavitação (p = 0,001) e consolidação (p = 0,003). A cavitação pulmonar foi um preditor independente de diagnóstico precoce (OR = 3,50; p = 0,028). Conclusões: Há necessidade de protocolos específicos para tuberculose nos serviços de emergência, não apenas para evitar atrasos no diagnóstico e no tratamento, mas também para modificar a dinâmica de transmissão da doença.

The clinical and molecular diagnosis of childhood and adolescent pulmonary tuberculosis in referral centers

Abstract INTRODUCTION: The diagnostic accuracy of Xpert MTB/RIF (Xpert) in pulmonary tuberculosis (PTB) in children is lower than in adults. In Brazil, the diagnosis of PTB is based on a diagnostic score system (DSS). This study aims to study the role of Xpert in children and adolescents with PTB symptoms. METHODS: A cross-sectional study was conducted in 3 referral centers to TB. Children and adolescents (0-19 years old) whose respiratory samples were submitted to Xpert were included. Statistical analysis (bivariate and logistic regression) to assess the simultaneous influence of TB-related variables on the occurrence of Xpert detectable in TB cases was done. To evaluate the agreement or disagreement between Xpert results with acid-fast bacillus (AFB) and cultures, κ method was used (significancy level of 5%). RESULTS: Eighty-eight patients were included in the study and PTB occurred in 43 patients (49%) and Xpert was detectable in 21 patients (24%). Adolescents and positive culture results were independent predictive variables of Xpert positivity. DSS sensitivity compared with the final diagnosis of TB was 100% (95% CI, 88.1-100%), specificity was 97.2% (95% CI, 85.5-99.9%). The accuracy of the method was 98.5% (95% CI, 91.7-99.9%). CONCLUSIONS: Xpert contributed to diagnosis in 9% of patients with AFB and in culture negative cases. DSS indicated relevance for this diagnostic approach of intrathoracic TB (ITB) in reference centers for presenting data both with high sensitivity and specificity.

Sintomáticos respiratorios en personas atendidas en establecimientos de salud del Ministerio de Salud en Lima, Perú / Respiratory symptoms in people attended in health facilities of the Ministry of Health in Lima, Peru

RESUMEN Objetivo. El objetivo de este estudio fue determinar el porcentaje de sintomáticos respiratorios (SR), según la definición programática, entre las personas que en condiciones habituales acuden a consulta en los establecimientos de salud de primer nivel del Ministerio de Salud en Lima, e identificar el porcentaje de pacientes con tuberculosis entre los SR y entre tosedores de más de siete días. Materiales y métodos. Estudio transversal en pacientes que acudieron a consulta en 57 centros de salud. Se identificó a los pacientes con tos y expectoración de más de siete días y SR, a quienes se les tomó una muestra de esputo para descarte de tuberculosis mediante baciloscopía y cultivos. Resultados. Se encuestaron 10 421 personas. El 2,7% presentaron tos con expectoración por ≥7 días y solo el 1,1% fueron SR; 215 pacientes fueron examinados para descarte de tuberculosis. Siete (5,9%) de los SR y ocho (4,8%) de los pacientes con tos de 7-14 días tuvieron tuberculosis. Conclusión. El porcentaje de SR en establecimientos de salud del Ministerio de Salud en Lima fue menor al 5% esperado, con un rango de 0,8% en Callao hasta 1,5% en Lima Ciudad. El porcentaje de tuberculosis entre tosedores de 7-14 días y SR concuerda con el hallado en otros estudios locales. Se debe considerar la posibilidad de disminuir la meta de SR a menos del 5% y ampliar el despistaje de tuberculosis a pacientes con tos ≥7 días en las Direcciones de Salud con altas incidencias de tuberculosis.

ABSTRACT Objective. The aim of this study was to determine the percentage of symptomatic respiratory (SR) cases, according to the programmatic definition, among people who attend medical offices at first-level health facilities of the Ministry of Health in Lima under normal circumstances. The study also aims at identifying the percentage of patients with tuberculosis among the RS and among coughers over seven days. Materials and Methods. Cross-sectional study of patients attending consultations at 57 health centers. Patients with cough and phlegm lasting more than seven days and RS were identified and a sputum sample was taken to rule out tuberculosis by smear and culture. Results. A total of 10,421 people was surveyed. A 2.7% had cough with phlegm for ≥7 days and only 1.1% were SR; 215 patients were screened for tuberculosis. Seven (5.9%) of the RS and eight (4.8%) of the patients with a 7-14-day cough had tuberculosis. Conclusions. The percentage of RS in the Ministry of Health's health facilities in Lima was less than the expected 5%, ranging from 0.8% in Callao to 1.5% in Lima City. The percentage of tuberculosis among coughers (lasting 7-14 days) and RS is consistent with the findings of other local studies. Consideration should be given to lowering the RS target to less than 5% and expanding tuberculosis screening to patients with cough ≥7 days at the Health Divisions with high tuberculosis incidence.

Genotipificación de aislamientos del complejo Mycobacterium tuberculosis mediante MIRU-VNTR, Cali, Colombia, 2013-2015 / MIRU-VNTR genotyping of Mycobacterium tuberculosis in a population of patients in Cali, Colombia, 2013-2015

Resumen Introducción. La tuberculosis continúa siendo uno de los problemas de salud más importantes a nivel mundial y, con la infección por el virus de la inmunodeficiencia humana (HIV), constituye la principal causa de muerte por infecciones. En el 2016, se notificaron 6,3 millones de casos nuevos de la enfermedad. Objetivo. Describir los patrones genéticos determinados mediante la genotipificación del número variable de repeticiones en tándem de unidades repetitivas interespaciadas de micobacterias (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats, MIRU-VNTR) en la población de estudio y compararlos con los hallados en otros estudios locales e internacionales. Materiales y métodos. Mediante MIRU-VNTR, entre el 2013 y el 2015 se hizo la genotipificación de 105 muestras de ADN extraídas del esputo o de aislamientos en cultivo de M. tuberculosis provenientes de pacientes residentes en Cali con diagnóstico de tuberculosis pulmonar. La amplificación de 24 loci MIRU-VNTR se hizo por medio de la reacción en cadena de la polimerasa (PCR). Los amplicones resultantes se visualizaron por electroforesis en geles de agarosa (2 %) teñidos con SYBR Safe™. La asignación de los alelos se hizo con un análisis gráfico con el programa GelAnalyzer 2010. Los resultados obtenidos se analizaron con el algoritmo UPGMA y se compararon con las bases de datos internacionales MIRU-VNTRplus y SITVITWEB. Resultados. Se genotipificaron por completo 62 de las muestras y se obtuvieron 58 perfiles diferentes de MIRU-VNTR. Al comparar con las bases de datos internacionales, su distribución por linajes fue la siguiente: 54,8 % para el LAM, 25,8 % para el Haarlem, 14,5 % para el S, 3,2 % para el Beijing y 1,6 % para el Cameroon. Los patrones MIRU-VNTR correspondieron a 20 tipos internacionales de MIRU (MIRU International Types, MIT) diferentes, y los más frecuentes fueron el MIT 190 y el MIT 110, con 22,6 y 6,5 %, respectivamente. Conclusión. Estos resultados confirmaron hallazgos previos sobre el predominio de los linajes LAM y Haarlem en la ciudad y la presencia de los MIT encontrados en otra ciudad de Colombia.

Abstract Introduction: Tuberculosis continues to be one of the main public health problems in the world. Together with the HIV infection, it is one of the main causes of death due to infections worldwide. In 2016, 6.3 million new cases of the disease were reported. Objective: To describe the genetic patterns determined by genotyping using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) in the study population and compare them with other studies carried out in Cali, Colombia, and the world. Materials and methods: We genotyped a total of 105 DNA samples extracted from sputum or culture isolates of the Mycobacterium tuberculosis complex, which were obtained from pulmonary tuberculosis diagnosed patients over the period 2013-2015, in Cali. We performed PCR amplification of 24 loci by MIRU-VNTR on the DNA extracted from the samples. The amplicons were visualized in agarose gel electrophoresis (2%) with SYBR Safe™ staining. Then, the alleles were designated by graphical analysis using the GelAnalyzer 2010 software. These results were analyzed using the UPGMA logarithm and compared with the registers from the MIRU-VNTR plus and SITVITWEB databases. Results: We genotyped 62 of the samples completely and we obtained 58 different MIRU-VNTR profiles. By comparing with the international databases, we determined the following distributions per lineage: LAM, 54.8%; Haarlem,25.8%; S, 14.5%; Beijing, 3.2%, and Cameroon, 1.6%. The MIRU-VNTR patterns corresponded to 17 different MITs; the most frequent were MIT 190 and MIT 110, with 22.6% and 6.5%, respectively. Conclusions: These results demonstrated previous observations about the predominance of the LAM and Haarlem lineages in the city, and the presence of the MITs found in another city of Colombia.

La importancia de investigar Mycobacterium bovis en muestras clínicas de procedencia humana / Importance of investigating Mycobacterium bovis in clinical samples of human origin

Resumen Introducción. La tuberculosis es una enfermedad infectocontagiosa que continúa siendo un problema mundial de salud pública. Es la principal causa de mortalidad en personas con HIV. Objetivo. Identificar la presencia de Mycobacterium bovis como agente etiológico de tuberculosis humana en muestras de esputo con baciloscopia positiva, mediante la prueba Genotype MTBC™. Materiales y métodos. Se llevó a cabo un estudio descriptivo de 88 muestras de esputo remitidas al Grupo de Micobacterias del Instituto Nacional de Salud entre enero y noviembre de 2015. Se hizo el análisis microbiológico convencional y se empleó la prueba molecular de Genotype MTBC™ para diferenciar las especies del complejo M. tuberculosis. Resultados. Sesenta y dos casos (70,5 %) correspondían a pacientes de sexo masculino; los grupos más afectados fueron el de 24 a 34 años, el de residentes en las cabeceras municipales, y el de afiliados al régimen subsidiado. En el 50 % (44) de las muestras con resultados en la prueba de identificación de la especie, se detectó el complejo M. tuberculosis. Conclusiones. La mayor carga de la enfermedad se registró en la población masculina y en edad productiva. La prueba de identificación para especies del complejo, solo demostró la presencia de M. tuberculosis. Sin embargo, con estos datos no es posible descartar M. bovis en humanos con tuberculosis en Colombia. La identificación diferencial de la especie debería implementarse de forma rutinaria en los casos de tuberculosis en los grupos de riesgo y en las zonas donde se conoce la circulación de esta micobacteria en bovinos.

Abstract Introduction: Tuberculosis is an infectious disease that still represents a major public health problem worldwide. It is one of the main causes of mortality in people with HIV. Objective: To identify the presence of M. bovis as an etiological agent of human tuberculosis in sputum smear positive samples using the test Genotype MTBC™. Materials and methods: We conducted a descriptive study, 88 sputum samples were submitted to the Grupo de Micobacterias of the Instituto Nacional de Salud between January and November, 2015. We used the conventional microbiological analysis and the molecular test Genotype MTBC™ to identify the M. tuberculosis complex species. Results: Sixty two (70.5%) were males; the most affected groups were those between 24 and 34 years old, those residing in the municipal seats and those affiliated to the subsidized health plans. In 50.0% (44) of the samples with a result in the species identification test, we detected M. tuberculosis. Conclusion: The highest burden of the disease was recorded among the male population in productive ages. The identification test for species of the complex showed all were M. tuberculosis. However, it is not possible to discard the presence of M. bovis in humans in Colombia. The differential identification of species should be done in risk groups and in areas where the circulation of this mycobacterium in cattle is known.

Concentrations of rifampicin in pre-dose samples in patients with pulmonary tuberculosis

ABSTRACT Rifampicin is used in both phases of treatment for tuberculosis. In chronic use, the short half-life and the self-induction of metabolism can decrease the levels of the drug below the minimal inhibitory concentration. The aim of the study was to investigate whether plasma concentrations of rifampicin are sustained above 0.5 µg/mL in patients with tuberculosis using 600 mg/day. Rifampicin was measured in plasma by high-performance liquid chromatography and a sputum smear microscopy was performed in all days of the study. A total of 44 male patients completed the study. On days 31, 61 and 91, the mean plasma concentrations of rifampicin were 0.6 (0.5) µg/mL, 0.55 (0.5) µg/mL and 0.46 (0.4) µg/mL. There was a high variation of rifampicin levels leading to a high percentage of samples with concentrations below 0.5 µg/mL. There was no significant association between the frequency of samples with drug levels below 0.5 µg/mL with the conversion of the sputum microscopy. These data suggest that pre-doses samples offer limited information on the exposure of M. tuberculosis to rifampicin.

Identificación y estudio de susceptibilidad antimicrobiana en cepas de mycobacterium spp. aisladas en un hospital de alta complejidad / Identification and study of antimicrobial susceptibility of isolated mycobacterium spp. strains in a hospital of high complexity

El género Mycobacterium se encuentra asociado a una cantidad importante de patologías, donde la tuberculosis destaca dentro de los principales problemas de salud pública a nivel mundial y nacional. Esta se agudiza con el incremento en la resistencia antimicrobiana y, por ello, la pesquisa de micobacterias contempla un pilar fundamental en el diagnóstico de patologías infecciosas de importancia clínica. Por lo tanto, el objetivo fue describir las principales especies de micobacterias aisladas y su patrón de susceptibilidad a partir de muestras clínicas procesadas en el Hospital Dr. Hernán Henríquez Aravena durante el año 2012. Se realizó un estudio descriptivo retrospectivo, en donde se utilizaron los resultados de 7023 baciloscopías procesadas en el Laboratorio Clínico del Hospital Dr. Hernán Henríquez Aravena de Temuco el año 2012. Todas las baciloscopías fueron analizadas y solicitadas según criterios establecidos por el Instituto de Salud Pública de Chile, comprendiendo muestras de expectoración y no expectoración. De las 7023 baciloscopías realizadas, 100 resultaron ser positivas para Mycobacterium. De 21 cepas enviadas al Instituto de Salud Pública de Chile para identificación, 19 cepas corresponden al complejo Mycobacterium tuberculosis y dos a Mycobacterium avium intracelular. En el estudio de sensibilidad, se encontró resistencia a estreptomicina e isoniazida en 13,3 % de las expectoraciones. De acuerdo a lo establecido por la literatura, más del 90 % pertenecen a Mycobacterium tuberculosis, mientras que, de las micobacterias no tuberculosas sólo se aislaron Mycobacterium avium intracelular. Los antimicrobianos con mayores niveles de resistencia son estreptomicina e isoniazida.

The genus Mycobacterium is associated with a significant number of pathologies, where tuberculosis stands out among the main public health problems worldwide and nationally. This is exacerbated by the increase in antimicrobial resistance and, therefore, the research of mycobacteria contemplates a fundamental pillar in the diagnosis of infectious pathologies of clinical importance. Therefore, the aim was to describe the main species of isolated mycobacteria and their susceptibility pattern from clinical samples processed at the Dr. Hernán Henríquez Aravena Hospital during 2012. A retrospective descriptive study was carried out, where the results of 7023 sputum microscopy processed in the Clinical Laboratory of the Dr. Hernán Henríquez Aravena Hospital in Temuco in 2012. All sputum microscopy was analyzed and requested according to criteria established by the Instituto de Salud Pública of Chile, including expectoration and non-sputum samples. Of the 7023-sputum microscopy performed, 100 were positive for Mycobacterium. Of 21 strains sent to the Instituto de Salud Pública of Chile for identification, 19 strains correspond to the Mycobacterium tuberculosis complex and two to intracellular Mycobacterium avium. In the sensitivity study, resistance to streptomycin and isoniazid was found in 13.3 % of the expectorations. According to what is established by the literature, more than 90 % belong to Mycobacterium tuberculosis, while only intracellular Mycobacterium avium was isolated from non-tuberculous mycobacteria. Antimicrobials with higher levels of resistance are streptomycin and isoniazid.

Therapeutic itinerary of people with tuberculosis in face with their health needs / Itinerario terapéutico de personas con tuberculosis ante sus necesidades de salud / Itinerário terapêutico de pessoas com tuberculose diante de suas necessidades de saúde

Abstract Objective: To describe the therapeutic itinerary of people with tuberculosis in face of their health needs. Method: Descriptive, qualitative study. Semi-structured interviews were carried out with ten patients. Hermeneutic-dialectic method of analysis and concept of therapeutic itinerary as driver of the analysis. Results: Most had classic symptoms at the beginning, however there was a case with coughing for more than one year. Entrance door, access to diagnosis and treatment were predominant in Primary Care, through smear microscopy and X-ray; patients had to pay for exams. Decentralization of treatment for other services when necessary or by link with the professional. The patient followed the decisions of the professionals and the support of relatives; prejudice regarding the disease was noted. Conclusions and implications for practice: Fragility in disease management, importance of bonding and family. It should be considered the impact of the disease and the need to support patients to ensure continuity of care.

Resumen Objetivo: Describir el itinerario terapéutico de personas con tuberculosis ante sus necesidades de salud. Método: Estudio descriptivo, cualitativo. Se realizaron entrevistas semiestructuradas con diez pacientes. Método de análisis hermenéutico-dialéctico y concepto de itinerario terapéutico como conductor del análisis. Resultados: La mayoría presentó síntomas clásicos al inicio, pero hubo un caso con tos durante más de un año. Puerta de entrada, acceso al diagnóstico y tratamiento fueron predominantes en la Atención Primaria, a través de baciloscopía y radiografía; se realizó un seguimiento de los exámenes por los pacientes. Descentralización del tratamiento para otros servicios cuando necesario o por vínculo con el profesional. Paciente siguió las decisiones de los profesionales y del apoyo de familiares; prejuicio con la enfermedad. Conclusiones e implicaciones para la práctica: Fragilidad en el manejo de la enfermedad, importancia del vínculo y de la familia. Se debe considerar el impacto de la enfermedad y la necesidad de apoyo a los pacientes para garantizar la continuidad de la atención.

Resumo Objetivo: Descrever o itinerário terapêutico de pessoas com tuberculose diante de suas necessidades de saúde. Método: Estudo descritivo, qualitativo. Realizadas entrevistas semiestruturadas com dez pacientes. Método de análise hermenêutica-dialética e conceito de itinerário terapêutico como condutor da análise. Resultados: A maioria apresentou sintomas clássicos no início da doença, mas houve caso com tosse por mais de um ano. Porta de entrada, acesso ao diagnóstico e tratamento foram predominantes na Atenção Primária, através de baciloscopia e raio-X; houve custeio de exames pelos pacientes. Descentralização do tratamento para outros serviços quando necessário ou por vínculo com o profissional. O paciente seguiu as decisões dos profissionais e do apoio de familiares; constatou-se preconceito relativo à doença. Conclusões e implicações para a prática: Fragilidade no manejo da doença, importância do vínculo e da família. Deve-se considerar o impacto da doença e a necessidade de apoio aos pacientes para garantir a continuidade da atenção.

Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing / Desempenho de testes para o diagnóstico de tuberculose pulmonar em populações indígenas no Brasil: a contribuição do Teste Rápido Molecular

ABSTRACT Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

RESUMO Objetivo: Avaliar a acurácia do teste rápido molecular como ferramenta diagnóstica e estimar a incidência de casos pulmonares positivos entre a população indígena. Métodos: Estudo epidemiológico baseado em dados secundários. Foi calculada a incidência de casos de tuberculose pulmonar positiva entre 1° de janeiro de 2011 e 31 de dezembro de 2016, e o desempenho da baciloscopia e do teste rápido molecular no diagnóstico de tuberculose pulmonar, em comparação à cultura de escarro (teste padrão). Resultados: Foram incluídos 4.048 casos de indígenas considerados sintomáticos respiratórios, que forneceram amostras de escarro para análise. Destes, 3,7%, 6,7% e 3,7% apresentaram resultados positivos para baciloscopia, cultura e teste rápido molecular, respectivamente. A incidência média de tuberculose pulmonar foi de 269,3/100 mil habitantes. A sensibilidade do teste rápido molecular, em relação à cultura, foi 93,1% e a especificidade foi 98,2%. A baciloscopia apresentou sensibilidade 55,1% e especificidade 99,6%. Conclusões: O teste rápido molecular pode ser útil em áreas remotas, com recursos limitados e incidência de tuberculose elevada, como as aldeias indígenas nas áreas rurais do país. Ademais, o teste rápido molecular apresenta como principais vantagens o fácil manuseio, os resultados rápidos e a possibilidade de identificar a resistência à rifampicina. Em conjunto, esses atributos facilitam o início do tratamento precoce, contribuindo para reduzir a transmissão em comunidades reconhecidamente vulneráveis à infecção e à doença.

Accuracy of a rapid molecular test for tuberculosis in sputum samples, bronchoalveolar lavage fluid, and tracheal aspirate obtained from patients with suspected pulmonary tuberculosis at a tertiary referral hospital / Acurácia do teste rápido molecular para tuberculose em amostras de escarro, lavado broncoalveolar e aspirado traqueal obtidos de pacientes com suspeita de tuberculose pulmonar em um hospital de referência terciária

ABSTRACT Tuberculosis continues to be a major public health problem worldwide. The aim of the present study was to evaluate the accuracy of the Xpert MTB/RIF rapid molecular test for tuberculosis, using pulmonary samples obtained from patients treated at the Júlia Kubitschek Hospital, which is operated by the Hospital Foundation of the State of Minas Gerais, in the city of Belo Horizonte, Brazil. This was a retrospective study comparing the Xpert MTB/RIF test results with those of standard culture for Mycobacterium tuberculosis and phenotypic susceptibility tests. Although the Xpert MTB/RIF test showed high accuracy for the detection of M. tuberculosis and its resistance to rifampin, attention must be given to the clinical status of the patient, in relation to the test results, as well as to the limitations of molecular tests.

RESUMO A tuberculose permanece como um grave problema de saúde pública. O objetivo deste estudo foi avaliar a acurácia do teste rápido molecular Xpert MTB/RIF em amostras pulmonares no Hospital Júlia Kubitschek, Fundação Hospitalar do Estado de Minas Gerais, localizado em Belo Horizonte (MG). Trata-se de um estudo descritivo retrospectivo, considerando-se como método padrão a cultura para o bacilo da tuberculose e o teste de sensibilidade fenotípico. O teste Xpert MTB/RIF apresentou ótima acurácia para a detecção da tuberculose e resistência à rifampicina, mas é necessária a atenção a dados clínicos do paciente em relação ao resultado do exame e às limitações dos testes moleculares.

Clinical impact and cost analysis of the use of either the Xpert MTB Rif test or sputum smear microscopy in the diagnosis of pulmonary tuberculosis in Rio de Janeiro, Brazil

Abstract INTRODUCTION: The molecular test Xpert MTB/RIF (Xpert) has been recommended for use in the diagnosis of pulmonary tuberculosis (PTB); however, data on the cost of incorporating it under routine conditions in high-burden countries are scarce. The clinical impact and costs incurred in adopting the Xpert test in routine PTB diagnosis was evaluated in a prospective study conducted from November 2012 to November of 2013, in the City of Rio de Janeiro, Brazil. METHODS: The diagnostic and therapeutic cascade for TB treatment was evaluated using Xpert in the first stage (S1), and sputum smear microscopy (SSM) in the second stage (S2). The mean costs associated with each diagnostic test were calculated including equipment, human resources, supplies, and infrastructure. RESULTS: We included 232 subjects with probable TB (S1 = 87; S2 = 145). The sensitivities of Xpert and SSM were 91.7% (22/24) and 79.1% (34/43), respectively. The median time between triage and TB treatment initiation in S1 (n = 24) was 14.5 days (IQR 8-28.0) and in S2 (n = 43) it was 8 days [interquartile range (IQR) 6-12.0]. The estimated mean costs per examination in S1 and S2 were US$24.61 and US$6.98, respectively. CONCLUSIONS: Compared with SSM, Xpert test showed a greater sensitivity, but it also had a time delay with respect to treatment initiation and a higher mean cost per examination.

Diagnóstico molecular de tuberculosis multidrogorresistente en muestras de esputo mediante el análisis de curvas de melting / Molecular diagnosis of multidrug-resistant tuberculosis in sputum samples by melting curve analysis

RESUMEN Objetivos. Analizar curvas de melting para el diagnóstico de tuberculosis multidrogorresistente a partir de muestras de esputo. Materiales y métodos. Se colectaron muestras de esputo (n = 250) de pacientes con sospecha clínica de tuberculosis pulmonar según resultado de baciloscopia y cultivados en medio sólido Lowenstein Jensen. Según el método de referencia se trabajó con 124 muestras sensibles a rifampicina e isoniacida, 24 resistentes a rifampicina, 33 resistentes a isoniacida y 69 multidrogorresistentes. Se evaluó por PCR en tiempo real y luego por las curvas de melting, se utilizó el gen rpoB como biomarcador de resistencia a rifampicina, y el gen katG y región promotora inhA como biomarcadores de resistencia a isoniacida. La cepa H37Rv fue considerada como control sensible a drogas. Se compararon los resultados del método de referencia y los resultados del análisis de curvas de melting para evaluar los parámetros de sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo. Resultados. La resistencia a rifampicina mostró una sensibilidad de 90,3 %, especificidad de 90,4 %, valor predictivo positivo de 84,8 % y valor predictivo negativo de 94,0 %. La resistencia a isoniacida mostró una sensibilidad de 90,2 %, especificidad de 93,9 %, valor predictivo positivo de 91,1 % y valor predictivo negativo de 93,3 %. La detección de tuberculosis multidrogorresistente mostró valores de 89,9 %, 90,6 %, 78,5 % y 95,9 % para sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo, respectivamente. Conclusiones. El análisis de curvas de melting mostró ser seguro y confiable para ser utilizado en el diagnóstico rápido de tuberculosis multidrogorresistente en muestras de esputo.

ABSTRACT Objectives. To analyze melting curves for the diagnosis of multidrug-resistant tuberculosis from sputum samples. Materials and Methods. Sputum samples (n = 250) were collected from patients with clinical suspicion of pulmonary tuberculosis as a result of bacilloscopy and cultured in solid medium Lowenstein Jensen. According to the reference method, 124 samples sensitive to rifampicin and isoniazid, 24 resistant to rifampicin, 33 resistant to isoniazid, and 69 multidrug-resistant were used. It was evaluated by real-time PCR and then by melting curves, the rpoB gene was used as a biomarker of rifampicin resistance, and the katG gene and inhA promoter region were used as biomarkers of isoniazid resistance. The H37Rv strain was considered a drug-sensitive control. The results of the reference method and the results of the melting curve analysis were compared to evaluate the parameters of sensitivity, specificity, positive predictive value and negative predictive value. Results. Rifampicin resistance showed a sensitivity of 90.3%, specificity of 90.4%, positive predictive value of 84.8% and negative predictive value of 94.0%. Isoniazid resistance showed a sensitivity of 90.2%, specificity of 93.9%, positive predictive value of 91.1% and negative predictive value of 93.3%. The detection of multidrug-resistant tuberculosis showed values of 89.9%, 90.6%, 78.5% and 95.9% for sensitivity, specificity, positive predictive value and negative predictive value, respectively. Conclusions. The melting curve analysis showed to be safe and reliable to be used in the rapid diagnosis of multidrug-resistant tuberculosis in sputum samples.

Rapid molecular test for tuberculosis: impact of its routine use at a referral hospital / Teste rápido molecular para tuberculose: avaliação do impacto de seu uso na rotina em um hospital de referência

ABSTRACT 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.

RESUMO Objetivo: Avaliar o impacto do teste rápido molecular automatizado Xpert MTB/RIF, utilizado para a detecção de Mycobacterium tuberculosis e sua resistência à rifampicina, em condições de rotina, em um hospital de referência no estado da Bahia. Métodos: Estudo descritivo retrospectivo utilizando o banco de dados do Laboratório de Micobacteriologia do Hospital Especializado Octávio Mangabeira, localizado na cidade de Salvador, e um programa de georreferenciamento. Entre junho de 2014 e março de 2015, foram incluídas no estudo 3.877 amostras de escarro coletadas de pacientes sintomáticos respiratórios em condições de rotina. Todas as amostras coletadas foram submetidas tanto à baciloscopia quanto a Xpert MTB/RIF. Os pacientes foram estratificados por sexo, idade e georreferenciamento. Resultados: Das 3.877 amostras de escarro analisadas, Xpert MTB/RIF detectou a presença de M. tuberculosis em 678 pacientes (17,5%). Desses, 60 (8,8%) apresentaram resistência à rifampicina. O Xpert MTB/RIF detectou 254 pacientes com baciloscopia negativa, representando um acréscimo diagnóstico de 59,9%. Conclusões: A implantação do Xpert MTB/RIF, sob condições de rotina, teve um impacto significativo no aumento da detecção de casos de tuberculose em pacientes com baciloscopia negativa.

Impact of smoking on sputum culture conversion and pulmonary tuberculosis treatment outcomes in Brazil: a retrospective cohort study / Impacto do tabagismo na conversão de cultura e no desfecho do tratamento da tuberculose pulmonar no Brasil: estudo de coorte retrospectivo

ABSTRACT 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 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; 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.

RESUMO Objetivo: Avaliar o impacto do tabagismo no desfecho do tratamento da tuberculose pulmonar (TBP) e na taxa de conversão da cultura de Mycobacterium tuberculosis no escarro ao final do segundo mês de tratamento em pacientes com TBP confirmada por cultura em um local com incidência de tuberculose moderada no Brasil. Métodos: Estudo de coorte retrospectivo envolvendo pacientes com TBP diagnosticados e tratados no Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro entre 2004 e 2012. Resultados: De 298 pacientes com diagnóstico confirmado de TBP no período do estudo, 174 foram incluídos na análise dos desfechos: 97 nunca fumaram (55,7%), 31 eram ex-tabagistas (17,8%), e 46 eram tabagistas atuais (26,5%). O tabagismo foi associado ao atraso na conversão da cultura do final do segundo mês do tratamento (risco relativo = 3,58 &091;IC95%: 1,30-9,86&093;; p = 0,01), assim como ao desfecho de tratamento não favorável (risco relativo = 6,29 &091;IC95%: 1,57-25,21&093;; p = 0,009). A associação entre tabagismo e cultura positiva ao final do segundo mês de tratamento foi estatisticamente significante entre os tabagistas atuais (p = 0.027). Conclusões: Nesta amostra, os pacientes tabagistas atuais apresentaram uma maior probabilidade de atraso na conversão da cultura após dois meses de tratamento e de desfecho de tratamento não favorável do que aqueles que nunca fumaram.