Enfermedad pulmonar por micobacterias no tuberculosas: análisis de 62 casos / Non-tuberculosis mycobacterial lung disease: Analyses of 62 cases

Introducción El objetivo de nuestro estudio fue evaluar la frecuencia de aislamiento de la infección respiratoria por micobacterias no tuberculosas (MNT) y analizar las características clínico-epidemiológicas de los pacientes infectados por MNT. Métodos Estudio observacional retrospectivo de 83 muestras respiratorias con aislamiento de MNT de 62 pacientes entre los años 2015 y 2021 en el Hospital General Universitario Doctor Balmis. Resultados Se cumplían criterios de infección respiratoria por MNT en 15 pacientes (24,2%). Las MNT más frecuentemente aisladas en los pacientes que cumplieron criterios de infección fueron las pertenecientes al complejo Mycobacterium avium complex (M. avium complex). De los 15 pacientes infectados, 11 (73,3%) presentaban comorbilidad respiratoria y la comorbilidad respiratoria más frecuente en los pacientes infectados fueron las bronquiectasias (5 pacientes; 45,5%). De los pacientes infectados se pautó tratamiento antibiótico dirigido en el 83,3% de los casos. Conclusión Uno de cada 7 pacientes con aislamiento por MNT cumplen criterios de infección. Se corrobora el papel principal de las especies de M. avium complex y la relevancia del daño estructural pulmonar en el desarrollo de enfermedad pulmonar por MNT (AU)

Introduction The objective of our study was to evaluate the frequency of isolation of respiratory infection by non-tuberculous mycobacteria (NTM) and to analyze the clinical-epidemiological characteristics of patients infected with NTM. Methods Retrospective observational study of 83 respiratory samples with NTM isolation from 62 patients between 2015 and 2021 at the Doctor Balmis General University Hospital. Results MNT respiratory infection criteria were met in 15 patients (24.2%). The most frequently isolated NTM's in patients who met infection criteria were those belonging to the Mycobacterium avium complex. Of the 15 infected patients, 11 (73.3%) had respiratory comorbidity and the most frequent respiratory comorbidity in infected patients was bronchiectasis (5 patients; 45.5%). Of the infected patients, targeted antibiotic treatment was prescribed in 83.3% of the cases. Conclusion One in 7 patients with NTM isolation meets infection criteria. The main role of the species of Mycobacterium avium complex is corroborated, and the relevance of lung structural damage in the development of lung disease due to NTM (AU)

[Non-tuberculosis mycobacterial lung disease: Analyses of 62 cases]. / Enfermedad pulmonar por micobacterias no tuberculosas: análisis de 62 casos.

INTRODUCTION: The objective of our study was to evaluate the frequency of isolation of respiratory infection by non-tuberculous mycobacteria (NTM) and to analyze the clinical-epidemiological characteristics of patients infected with NTM. METHODS: Retrospective observational study of 83 respiratory samples with NTM isolation from 62 patients between 2015 and 2021 at the Doctor Balmis General University Hospital. RESULTS: MNT respiratory infection criteria were met in 15 patients (24.2%). The most frequently isolated NTM's in patients who met infection criteria were those belonging to the Mycobacterium avium complex. Of the 15 infected patients, 11 (73.3%) had respiratory comorbidity and the most frequent respiratory comorbidity in infected patients was bronchiectasis (5 patients; 45.5%). Of the infected patients, targeted antibiotic treatment was prescribed in 83.3% of the cases. CONCLUSION: One in 7 patients with NTM isolation meets infection criteria. The main role of the species of Mycobacterium avium complex is corroborated, and the relevance of lung structural damage in the development of lung disease due to NTM.

Ocular Tuberculosis – A Portuguese Portrait of This Rare and Challenging Problem / Tuberculosis ocular: un retrato portugués de este problema raro y desafiante

Objectives: Although threatening there is not enough awareness for ocular tuberculosis, hence we intend to study and characterize the ocular tuberculosis observed on a Portuguese specialized pulmonology diagnostic center. Materials and Methodologies: Retrospective study of individuals diagnosed with ocular tuberculosis and followed up from 1st January2016 until 31th December 2018. Results: We studied 38 patients with presumed ocular tuberculosis, with mean age 53,315,7 years old, whose 55,3% were females. Only one patient had known immunosuppression, seven patients had history of previous tuberculosis and only two patients reported a known risk contact. None had extraocular disease. All patients had at least one positive immunologic test, either tuberculin skin test (63,2%) or Interferon Gamma Release Assay test (86,8%). Most patients presented bilateral ocular tuberculosis (44,7%). The standard four-drug regimen was the treatment of choice and corticosteroids were administered to 55,3% patients with no differences in treatment outcomes. The mean length of treatment was 8,6 months and among the patients who completed treatment, 72,4% presented clinical improvement or remission of the ocular manifestations. Conclusions: Ocular tuberculosis, despite a rare condition, carries a huge burden in health care centers. Delay in starting proper treatment can result in permanent blindness and impairment of life’s quality. This condition is probably underdiagnosed and, to our knowledge, there are no recent studies characterizing the latest trend of ocular tuberculosis in Portugal. (AU)

Objetivos: Aunque amenazante, no hay suficiente conciencia sobre la tuberculosis ocular, por lo que pretendemos estudiar y caracterizar los casos de tuberculosis ocular observados en un centro portugués de diagnóstico especializado en neumología. Materiales y Metodologías: Estudio retrospectivo de individuos con tuberculosis ocular seguidos desde 1 de enero de 2016 hasta 31 de diciembre de 2018. Resultados: Se estudiaron 38 pacientes, con una edad media de 53,3±15,7 años, de los cuales el 55,3% eran mujeres. Solo un paciente tenía inmunosupresión iatrogénica, siete pacientes tenían antecedentes de tuberculosis previa y dos pacientes reportaron un contacto de riesgo conocido. Ninguno tenía enfermedad extraocular. Todos los pacientes tenían al menos una prueba inmunológica positiva, ya sea prueba cutánea de tuberculina (63,2%) o prueba de interferón gamma (86,8%). La mayoría de los pacientes presentaron patología bilateral (44,7%). El régimen de cuatro fármacos fue el tratamiento de elección y se administraron corticoides al 55,3% de los pacientes sin diferencias en los resultados. La duración del tratamiento fue de 8,6 meses y entre los que completaron tratamiento, 72,4% presentó mejoría clínica o remisión. Conclusión: La tuberculosis ocular, aunque una condición rara, sobrecarga los centros de salud. El retraso en el inicio del tratamiento puede provocar ceguera y deterioro de la calidad de vida. Esta condición probablemente está subdiagnosticada y, hasta donde sabemos, no hay estudios que caractericen su evolución en Portugal. (AU)

Abscesos mamarios múltiples por Mycobacterium abscessus en mastopexia secundaria con implantes mamarios / Multiple breast abscesses due to Mycobacterium abscessus in secondary mastopexy with breast implant

Las infecciones periprotésicas son una complicación poco frecuente en cirugía de implantes mamarios, pero de difícil resolución si son causadas por gérmenes como las micobacterias. Mycobacterium abscessus es una micobacteria no tuberculosa de rápido crecimiento, que se presenta de manera atípica, generando abscesos y fístulas cutáneas. En este reporte presentamos el caso de una paciente que fue intervenida por recambio de implantes mamarios y mastopexia secundaria. La paciente presentó un seroma temprano como manifestación inicial y posteriormente desarrolló múltiples abscesos en todo el parénquima mamario. El tratamiento instaurado en la paciente fue la extracción del implante mamario,curaciones diarias de la herida, antibioticoterapia prolongada y punciones periódicas guiadas por ecografía, con cultivo del material obtenido. El objetivo de nuestro reporte fue presentar esta complicación generada por un germen poco frecuente, su forma de presentación, diagnóstico y el tratamiento establecido

Although periprosthetic infections are a rare complication in breast implant surgery, they are difficult to resolve if they entail germs like mycobacteria. Mycobacterium abscessus is a rapidly growing, nontuberculous mycobacterium that occurs atypically and generates abscesses and cutaneous fistulas. In this report, we present the case of a patient that underwent surgery for a breast implant replacement and a secondary mastopexy. The initial manifestation the patient evinced was an early seroma. Later, she developed multiple abscesses in all the breast parenchyma. The treatment established for the patient involved extracting the breast implant, daily cleaning and dressing of the wound, prolonged antibiotic therapy, and periodical punctures guided by ultrasound, accompanied by culture sampling. The aim of this report is to present this infrequent germ-generated complication, its form of manifestation, its diagnosis, and the established treatment.

Linfadenitis por Mycobacterium lentiflavum / Lymphadenitis caused by Mycobacterium lentiflavum

La linfadenitis cervical es la infección por micobacterias no tuberculosas (MNT) más frecuente en niños inmunocompetentes menores de 5 años. La mayoría de los casos a nivel mundial se debe a Mycobacterium avium complex (MAC). Mycobacterium lentiflavum (M. lentiflavum) se ha considerado una causa rara de MNT causante de linfadenitis. Presentamos dos casos de linfadenitis cervical y preauricular atendidos en un centro de salud de Madrid durante los años 2019-2020, que persisten a pesar de tratamiento antibiótico. Se realizaron test sanguíneos, serología, así como radiografía de tórax y prueba de tuberculina. Con la sospecha diagnóstica de MNT, los pacientes fueron derivados a un hospital terciario, donde se aisló M. lentiflavum. Aunque la actual evidencia acerca del tratamiento para la resolución de la linfadenitis es la escisión quirúrgica completa, en este caso fue descartada por la localización de los nódulos y el riesgo de dañar el nervio facial y la glándula parótida. Debido a que M. lentiflavum es resistente a la mayoría de los fármacos antituberculosos, se decidió, de acuerdo con los padres, un tratamiento conservador. Concluimos que M. lentiflavum debe ser considerado un importante patógeno emergente causante de linfadenitis y debe sospecharse en un paciente con una única linfadenitis cervical o preauricular que persiste a pesar de tratamiento antibiótico (AU)

Cervical lymphadenitis is the most common infection caused by non-tuberculous mycobacteria (NTM) in immuno-competent children under 5 years. Most cases of NTM associated cervical lymphadenitis worldwide are caused by Mycobacterium avium complex (MAC). Mycobacterium lentiflavum (M. lentiflavum) has been considered a rare cause of NTM associated lymphadenitis. We present two case reports of cervical and pre-auricular lymphadenitis managed in primary care in the Region of Madrid (Spain), between 2019-2020, that persisted despite antibiotic treatment. Routine blood tests, chest x-ray and tuberculin skin test were performed. As NTM was suspected, patients were referred to a tertiary hospital, where they underwent ultrasound guided aspiration, which cultured M. lentiflavum. Although, the first line treatment for NTM lymphadenitis is complete surgical excision, in these cases the proximity of the lymph nodes to the facial nerve and parotid gland meant this was not an option. Instead, a conservative approach of watch-and-wait was chosen in collaboration with the parents, as M. lentiflavum is resistant to most antituberculosis drugs. We conclude that M. lentiflavum should be considered as an important emergent pathogen causing cervical lymphadenitis, especially in cases with a single cervical or pre-auricular lymphadenitis resistant to antibiotic treatment. (AU)

Multidrug-resistant Mycolicibacterium fortuitum infection in a companion cat (Felis silvestris catus) in Brazil.

Mycolicibacterium fortuitum is a fast-growing bacterium and an opportunistic pathogen implicated in human and animal infections. Here we report the first case and genetic characterization of a strain of M. fortuitum isolated from skin lesions of a companion cat with atypical cutaneous mycobacteriosis in Brazil. In addition, the genome of this strain was sequenced, representing the first genome of this opportunistic pathogen isolated from an animal infection. The in silico and in vitro analysis regarding antibiotic resistance of this strain showed an intrinsic multiresistance antibiotic profile. However, this strain showed sensitivity to amikacin and ciprofloxacin, and the cat was treated long-term with these drugs.

Use of MALDI-TOF MS (Bruker Daltonics) for identification of Mycobacterium species isolated directly from liquid medium / Utilización de MALDI-TOF MS (Bruker Daltonics) para la identificación de micobacterias aisladas directamente en medio líquido

Objectives: The aim of this study was to describe the evaluation of the use of MALDI-TOF MS for the identification of non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis directly from liquid MGIT cultures from January 2017 to December 2017. Material/methods: A total of 155 isolates (mainly respiratory) were analyzed by MALDI-TOF MS (Bruker Daltonics) directly from MGIT liquid medium with a previous extraction procedure. Results: MALDI-TOF MS generated acceptable scores for 152 isolates (98.06%). Fifty isolates were identified as M. tuberculosis complex and the remaining 105 as NTM (M. abscessus subsp. abscessus, M. avium, M. celatum, M chelonae, M. chimaera, M. fortuitum, M. gordonae, M. intracellulare, M. kansasii, M. lentiflavum, M. mageritense, M. mucogenicum and M. xenopi). Conclusions: These results indicate that MALDI-TOF MS can be useful to identify mycobacteria directly from MGIT cultures and is an accurate, rapid and cost-effective system to be used as a routine method.(AU)

Introducción: Evaluamos la espectrometría de masas (MALDI-TOF MS [Bruker Daltonics]) para la identificación de micobacterias no tuberculosas (MNT) y Mycobacterium tuberculosis a partir de cultivos líquidos (MGIT) desde enero del 2017 a diciembre del 2017. Métodos: Se analizaron mediante MALDI-TOF MS 155 cultivos MGIT positivos, principalmente de origen respiratorio. Previamente a la realización de MALDI-TOF se realizó un procedimiento de extracción directamente del MGIT. Resultados: Mediante MALDI-TOF MS se identificó correctamente a partir del MGIT el 98,06% (n=152) de los aislados. Cincuenta aislados se identificaron como M. tuberculosis complex y los 105 restantes como MNT (M. abscessus subsp. abscessus, M. avium, M. celatum, M chelonae, M. chimaera, M. fortuitum, M. gordonae, M. intracellulare, M. kansasii, M. lentiflavum, M. mageritense, M. mucogenicum y M. xenopi). Conclusiones: Estos resultados indican que MALDI-TOF es una técnica precisa, rápida y coste-efectiva para identificar micobacterias directamente a partir de medios de cultivo líquidos en la rutina diaria.(AU)

Use of MALDI-TOF MS (Bruker Daltonics) for identification of Mycobacterium species isolated directly from liquid medium.

OBJECTIVES: The aim of this study was to describe the evaluation of the use of MALDI-TOF MS for the identification of non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis directly from liquid MGIT cultures from January 2017 to December 2017. MATERIAL/METHODS: A total of 155 isolates (mainly respiratory) were analyzed by MALDI-TOF MS (Bruker Daltonics) directly from MGIT liquid medium with a previous extraction procedure. RESULTS: MALDI-TOF MS generated acceptable scores for 152 isolates (98.06%). Fifty isolates were identified as M. tuberculosis complex and the remaining 105 as NTM (M. abscessus subsp. abscessus, M. avium, M. celatum, M chelonae, M. chimaera, M. fortuitum, M. gordonae, M. intracellulare, M. kansasii, M. lentiflavum, M. mageritense, M. mucogenicum and M. xenopi). CONCLUSIONS: These results indicate that MALDI-TOF MS can be useful to identify mycobacteria directly from MGIT cultures and is an accurate, rapid and cost-effective system to be used as a routine method.

Detección de anticuerpos anti-Mycobacterium avium subsp. paratuberculosis (MAP) en venados silvestres en Colombia / Detection of anti-Mycobacterium aviumsubsp. paratuberculosis antibodies in wild deer in Colombia

RESUMEN Objetivo. Determinar la presencia de anticuerpos anti-Mycobacterium avium subsp. paratuberculosis (MAP) en venados de cola blanca (Odocoileus virginianus) y venados de páramo (Mazama rufína), capturados en las regiones de la Orinoquía y el Caribe en Colombia. Materiales y métodos. Un total de 44 muestras de suero sanguíneo de venados de las especies M. rufína y O. virginianus fueron colectadas en condiciones de campo entre 2014 y 2016. Se utilizó un kit comercial de ELISA para la detección de anticuerpos anti-MAP. Un animal se consideró positivo a ELISA cuando la relación muestra-positivo (S/P%) fue > 0.4, según lo recomendado por el fabricante. Resultados. El 50% (22/44) de los animales muestreados resultaron positivos, lo que corresponde a 10 hembras y 12 machos. Un 81.8% (18/22) y un 77.3% (17/22) de estos animales seropositivos fueron capturados en la región de la Orinoquía y fueron reportados como adultos, respectivamente. Conclusiones. No se sabe cómo o cuándo se introdujo MAP en la población de ciervos colombianos en las regiones de estudio. La hipótesis más plausible para explicar la presencia de anticuerpos anti-MAP en estas poblaciones silvestres es la transmisión por contacto con el ganado bovino infectado, ya que en ambas regiones estas especies comparten pasturas. Este es el primer estudio en explorar la infección por MAP en animales silvestres en Colombia. Estos hallazgos respaldan la necesidad de realizar más estudios utilizando técnicas de diagnóstico directo, y aproximaciones investigativas que permitan la definición de vínculos en la dinámica de la infección entre mamíferos silvestres y domésticos en Colombia.

ABSTRACT Objective. To determine the presence of anti-Mycobacterium avium subsp. paratuberculosis (MAP) antibodies in white-tailed deer (Odocoileus virginianus) and red brocket deer (Mazama rufína), captured in the Orinoquía and Caribbean regions in Colombia. Materials and methods. A total of 44 blood serum samples from deer of species M. rufina and O. virginianus were collected under field conditions between 2014 and 2016. An ELISA commercial kit was used to detect anti-MAP antibodies. An animal was considered ELISA-positive at a sample-to-positive ratio (S/P%) of > 0.4, as recommended by the manufacturer. Results. The 50% (22/44) of the animals were positive, corresponding to 10 females and 12 males. An 81.8% (18/22) and 77.3% (17/22) of these seropositive animals were captured in the Orinoquía region and were reported as adults, respectively. Conclusions. It is not known how or when MAP was introduced in the Colombian deer population in the study regions. The most plausible hypothesis to explain the presence of antibodies against MAP in these wild populations is transmission by contact with infected bovine cattle since, in both regions, these species share pastures. This is the first study to explore MAP infection in wild animals in Colombia. These findings support the need for further studies using different direct diagnostic techniques and research approaches that allow the definition of links in the infection dynamics between wild and domestic mammals in Colombia.

Mycobacterium abscessus urinary tract infection: case report / Infecção urinária por Mycobacterium abscessus: relato de caso

Abstract Urinary tract infection is a serious public health issue that predominantly affects women. In men, it is more often associated with prostatic hyperplasia and bladder catheterization. Urogenital tuberculosis presents with nonspecific with nonspecific symptoms and the diagnosis can be made in the presence of sterile leukocyturia and recurrent infection with acid urine. Non-tuberculous mycobacteria or other non-tuberculosis mycobacteria are opportunistic pathogens that inhabit the soil, water or environment surfaces, and usually cause diseases in immunocompromised individuals. Mycobacterium abscessus is an agent that causes lung, skin and soft tissue hospital infections. Urinary tract infections by this pathogen are rare.

Resumo Infecção do trato urinário é um sério problema de saúde pública que acomete predominantemente as mulheres. Em homens, está mais relacionada com hiperplasia prostática e cateterismo vesical. A tuberculose urogenital cursa com sintomas inespecíficos e o diagnóstico pode ser aventado na presença de leucocitúria estéril, e infecção recorrente com urina ácida. Micobactérias não tuberculosas ou mycobacteria other than tuberculosis são patógenos oportunistas que habitam o solo, a água ou superfícies do meio ambiente, e geralmente causam doenças em imunodeprimidos. Mycobacterium abscessus é um agente que causa infecções nosocomiais, pulmonares, de pele e de tecidos moles. Infecção urinária decorrente desse patógeno é considerada rara.

Anal mycobacterial infections / Infecções micobacterianas do ânus

Abstract Background Mycobacterial infections are a serious public health problem worldwide. Involvement of the anal canal and perineum is very rare, but constitute an important differential diagnosis with other equally serious pathologies that may affect the region, such as malignant neoplasms and Crohn's disease. Objectives To conduct a literature review on mycobacterial infections of the perianal region considering the most recent information for diagnostic and therapeutic guidance of this disease. Methods Research was performed on the PUBMED and LILACS databases with the expressions Mycobacterium, Anal, Infection and Tuberculosis. We reviewed articles referring to series of treated cases, clinical reports and literature review published since 2005. Results Information was compiled on the epidemiology of mycobacterial infections; the clinical behavior of affected individuals; diagnostic options and their validity in clinical practice; and, finally, therapeutic options. Conclusions Mycobacterial infections of the anus and perineum are rare. The most common clinical presentations are the presence of ulceration and fistulization. The diagnosis involves more than one procedure for identifying the bacilli and should consider the presence of manifestations in more than one organ. The treatment is based on pharmacological intervention. Surgery is recommended for acute complications or chronic sequelae of the disease.

Resumo Introdução Infecções micobacterianas constituem um grave problema de saúde pública a nível mundial. As manifestações anoperineais são raras, mas constituem um importante diagnóstico diferencial com outras patologias igualmente graves que podem acometer a região, como as neoplasias malignas e a doença de Crohn. Objetivos Realizar um levantamento da literatura sobre infecções micobacterianas da região anoperineal, considerando as informações mais atuais para orientação diagnóstica e terapêutica dessa enfermidade. Métodos Foi realizada pesquisa nos bancos de dados PUBMED e LILACS com as expressões Mycobacterium, Anal, Infection e Tuberculosis. Foram revisados artigos referentes a séries de casos tratados, relatos clínicos e revisão da literatura publicada a partir de 2005. Resultados Foram compiladas informações sobre a epidemiologia das infecções micobacterianas; o comportamento clínico dos indivíduos afetados; opções diagnósticas e sua validade na prática clínica; e, por fim, opções terapêuticas. Conclusões Infecções micobacterianas da região anoperineal são raras. As apresentações clínicas mais comuns são a formação de ulceras e a fistulização. O diagnóstico envolve mais de um procedimento para identificação dos bacilos, e deve considerar a presença de manifestações em mais de um órgão. O tratamento é principalmente medicamentoso, sendo a cirurgia recomendada nas complicações agudas ou sequelas crônicas da doença.

Ocorrência de Micobactérias Não Tuberculosas (MNT) em uma unidade de referência do estado do Pará, Brasil / Occurrence of Nontuberculosis Mycotherapies (NTM) in a reference unit of the state of Pará, Brazil

Objetivo: Investigar a ocorrência de micobactérias não tuberculosas (MNT) em uma Unidade de Referência no Estado do Pará, Brasil e apresentar o perfil sociodemográfico e clínico dos pacientes acometidos. Métodos: foi realizada pesquisa descritiva retrospectiva com abordagem quantitativa por meio da coleta de dados no sistema de informação do laboratório que atua como referência para tuberculose nos vinte municípios da região Oeste do Pará no período de abril de 2011 a abril de 2017. Resultados: foram analisadas amostras de 513 pacientes com suspeita de TB, 09 (1,75%) tiveram diagnóstico de MNT, sendo isolados M. avium, M. asiaticum, M. intracellulare, M. paraensis e M. abscessus subsp. bolletii. Conclusão: evidencia­se o potencial das MNT em provocar doença semelhante à tuberculose, havendo a necessidade de melhorar a investigação etiológica para a detecção precoce das micobacterioses, afim de que sejam tomadas medidas adequadas de tratamento e prevenção da transmissão.

Objective: To investigate the occurrence of non­ tuberculous mycobacteria (NTM) in a Reference Unit in the State of Pará, Brazil, and present the sociodemographic and clinical profile of the patients affected. Methods: retrospective descriptive research was carried out using a quantitative approach through the data collection of the laboratory information system which acts as a reference for tuberculosis in the twenty municipalities of the western region of Pará from April 2011 to April 2017. Results: samples from 513 patients with suspected TB were analyzed, 09 (1.75%) were diagnosed with NTM , M. avium, M. asiaticum, M. intracellulare, M. paraenses and M. abscessus subsp. bolletii. Conclusion: the potential of MNT to provoke tuberculosis­like disease is evident, and there is a need to improve epidemiological investigation for the early detection of mycobacteriosis, so that appropriate treatment and prevention measures are taken.

Características clínicas e epidemiológicas de casos de infecção pulmonar por Mycobacterium kansasii no Rio de Janeiro, no período de 2006 a 2016 / Clinical and epidemiological characteristics of M. kansasii pulmonary infections from Rio de Janeiro, Brazil, between 2006 and 2016

RESUMO Objetivo Avaliar características clínicas, tomográficas e microbiológicas dos pacientes com doença pulmonar causada pela M. kansasii (DPMK) atendidos em unidade ambulatorial no período 2006-2016. Métodos Estudo descritivo, em que foram analisados 38 pacientes. Foram analisadas as características demográficas, clínico-radiológicas, laboratoriais e terapêuticas. Resultados A média de idade foi 64 anos (DP=10,6; IIQ=57-72; mediana=65,0) e 22 (57,9%) eram pacientes do sexo masculino. Comorbidade pulmonar estava presente em 89,5%. A comorbidade mais frequente foi a bronquiectasia (78,9%). Tratamento anterior para tuberculose pulmonar (TBP) foi relatado em 65,9%. O esquema terapêutico mais utilizado foi rifampicina, isoniazida e etambutol (44,7%). A tomografia de tórax (TCT) mostrou bronquiectasia (94,1%), distorção arquitetural (76,5%), espessamento de septo (67,6%) e cavidades (64,7%). A doença foi bilateral em 85,2%. Houve 10,7% de resistência à rifampicina, 67,9% resistentes ao etambutol e sensibilidade à claritromicina. Conclusão Em pacientes com doença pulmonar estrutural, é importante a busca de DPMNT, principal diagnóstico diferencial com TBP. TC de tórax demonstra diferentes padrões que se sobrepõem ao de doença estrutural causada por TBP ou outras enfermidades pulmonares. Destaca-se a resistência ao etambutol, fármaco componente do esquema preconizado.

ABSTRACT Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.

Pulmonary nontuberculous mycobacterial infections: presumptive diagnosis based on the international microbiological criteria adopted in the state of São Paulo, Brazil, 2011-2014 / Micobacterioses pulmonares: diagnóstico presuntivo pelos critérios microbiológicos internacionais adotados no estado de São Paulo, Brasil, 2011-2014

ABSTRACT Objective: Pulmonary nontuberculous mycobacterial infections are caused by nontuberculous mycobacteria (NTM), the microbiological diagnosis of which involves the isolation and identification of the same species in at least two sputum samples, one BAL fluid sample, or one lung biopsy sample. The objective of the present study was to determine the frequency at which the various NTM species are identified among selected individuals and in potential cases of pulmonary nontuberculous mycobacterial infection. Methods: This was a retrospective analysis of the data on species isolated from respiratory specimens collected from 2,843 individuals between 2011 and 2014. Potential NTM infection cases were identified on the basis of the international microbiological criteria adopted in the state of São Paulo. Results: A total of 50 species were identified using the molecular method PCR-restriction enzyme analysis. Samples collected from 1,014 individuals were analyzed in relation to the microbiological criteria, and 448 (44.18%) had a presumptive diagnosis of pulmonary nontuberculous mycobacterial infection, the species identified most frequently being, in descending order, Mycobacterium kansasii, M. abscessus, M. intracellulare, M. avium, and M. szulgai. Conclusions: Although various NTM species were identified among the individuals studied, those presumptively identified most frequently on the basis of the microbiological criteria adopted in the state of São Paulo were the ones that are most commonly associated with pulmonary nontuberculous mycobacterial infection worldwide or in specific geographic regions.

RESUMO Objetivo: As micobacterioses pulmonares são doenças causadas por micobactérias não tuberculosas (MNTs), cujo diagnóstico microbiológico envolve o isolamento e a identificação da mesma espécie a partir de pelo menos duas amostras de escarro, uma de lavado brônquico ou uma de biópsia pulmonar. O objetivo do presente estudo foi determinar as frequências das diferentes espécies de MNTs em indivíduos selecionados e em potenciais casos de micobacterioses pulmonares. Métodos: Análise retrospectiva dos dados de identificação de espécies isoladas a partir de espécimes clínicos pulmonares de 2.843 indivíduos incluídos no estudo entre 2011 e 2014. A identificação dos potenciais casos baseou-se nos critérios microbiológicos internacionais adotados no estado de São Paulo. Resultados: Um total de 50 espécies foi identificado utilizando-se o método molecular PCR-restriction enzyme analysis. Dos 1.014 indivíduos analisados quanto aos critérios microbiológicos, 448 (44,18%) tiveram o diagnóstico presuntivo de micobacteriose pulmonar, sendo as maiores frequências de casos, em ordem decrescente, Mycobacterium kansasii, M. abscessus, M. intracellulare, M. avium e M. szulgai. Conclusões: Embora tenham sido identificadas diversas espécies de MNTs entre os indivíduos estudados, as que tiveram as maiores frequências de casos presuntivamente identificados pelos critérios microbiológicos adotados no estado de São Paulo foram as que mais frequentemente estão associadas a micobacterioses pulmonares mundialmente ou em várias regiões geográficas.

Opções farmacológicas para ceratite por micobactérias não-tuberculosas: uma revisão integrativa / Pharmacological options for nontuberculous mycobacterial keratitis: an integrative review"

Introdução: as ceratites são infecções da córnea, que acontecem pós-trauma, cirúrgico ou não, ou em indivíduos imunossuprimidos e que podem ter como agente etiológico micobactérias não-tuberculosas (MNTs). O diagnóstico das ceratites por MNTs é feito pelos aspectos clínicos em associação à identificação do patógeno. Não existe um consenso na literatura com relação ao tratamento farmacológico. Objetivos: o objetivo primário é identificar as opções terapêuticas farmacológicas para ceratites por MNTs e, o secundário, descrever os aspectos clínicos dessa infecção. Metodologia: um total de 214 artigos foram encontrados através da pesquisa nas fontes CAPES, LILACS, PUBMED e Biblioteca Cochrane, utilizando-se as combinações de palavras chave: "ceratite" e "micobactérias não-tuberculosas, destes, após o uso dos critérios de exclusão, 4 artigos foram selecionados. Resultados: partindose das 4 publicações selecionadas foram reunidos 5 casos clínicos, todos com história de trauma corneano, cirúrgico ou não. Os 5 pacientes foram submetidos à técnica diagnóstica não-invasiva e em todos foi identificada MNT. Os tratamentos farmacológicos foram feitos com antimicrobianos das classes das quinolonas, aminoglicosídeos e macrolídeos. Em um dos casos foi usado um corticoide e em dois foi feita associação com anti-inflamatório não-esteroide. Conclusão: o tratamento farmacológico da ceratite por MNTs é de longo prazo, e, neste estudo, variou de 3 semanas a 6 meses. Os quimioterápicos usados são os aminoglicosídeos, macrolídeos e quinolonas e, em alguns casos, a combinação destes. O uso de anti-inflamatórios não-esteroidais e esteroidais não é consensual. Quanto aos aspectos clínicos, observam-se características comuns a outras ceratites infecciosas

Nontuberculous mycobacterial lung disease in a high tuberculosis incidence setting in Brazil / Doença pulmonar por micobactérias não tuberculosas em uma região de alta incidência de tuberculose no Brasil

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

RESUMO Objetivo: A incidência de doença pulmonar causada por micobactérias não tuberculosas (MNT) tem aumentado em todo o mundo. No Brasil, há poucos estudos sobre doença pulmonar por MNT, e sua prevalência ainda não é conhecida. Nosso objetivo foi determinar a etiologia específica da doença no estado do Rio Grande do Sul, bem como a frequência e a diversidade das espécies de MNT em nossa amostra de pacientes. Métodos: Análise retrospectiva dos prontuários de pacientes diagnosticados com doença pulmonar por MNT atendidos em um centro de referência localizado na cidade de Porto Alegre, RS, entre 2003 e 2013. Resultados: Nossa amostra foi composta por 100 pacientes. As espécies de MNT mais prevalentes foram Mycobacterium avium complex (MAC, complexo M. avium), em 35% dos casos; M. kansasii, em 17%; e M. abscessus, em 12%. Um total de 85 pacientes havia feito tratamento anterior para tuberculose. Condições associadas incluíram anormalidades estruturais nos pulmões, como bronquiectasias, em 23% dos casos; DPOC, em 17%; e condições imunossupressoras, como AIDS, em 24%. Conclusões: MAC e M. kansasii foram as espécies mais prevalentes envolvidas na doença pulmonar por MNT no estado, à semelhança do que ocorre em outras regiões do Brasil. Dados sobre a epidemiologia regional da doença pulmonar por MNT, sua etiologia específica e condições associadas são fundamentais para se estabelecer um tratamento adequado, já que cada espécie requer um esquema específico. A maioria dos pacientes com doença pulmonar por MNT havia feito tratamento anterior para tuberculose, o que pode levar a desenvolvimento de resistência e diagnóstico tardio.

Mycobacterium marinum: reporte de un caso / Mycobacterium marinum: a case report

El Mycobacterium marinum es un tipo de micobacteria no tuberculosa (NTM). La infección por esta bacteria es frecuente en peces de agua dulce o salada y muy raramente, suele causar infecciones en la población humana. Presentamos el caso de un paciente varón de 60 años, que consulta por placa ulcerosa en dorso de mano izquierda. El estudio histopatológico de biopsia informa: hiperplasia epitelial con un denso infiltrado en dermis y escasos granulomas con células gigantes. Se solicitan distintas pruebas, siendo únicamente positiva el PCR para Mycobacterium marinum, por lo que se procede a instaurar regimen antimicrobiano con evolución favorable. El contagio por esta bacteria, se produce por inoculación directa del microorganismo, a través de heridas o erosiones cutáneas o por mordeduras de peces contaminados. Las formas de presentación clínica varían, siendo la más común la presencia de pápulas o nódulos solitarios en dedos o manos. También se puede manifestar en forma de linfangitis proximal o esporotricoide, extensión a órganos profundos y patrón esporotricoide facial. El diagnóstico requiere un alto índice de sospecha, debido a que la frecuencia de esta afección es muy baja, siendo de 0.04 a 0.27 por cada 100.000 habitantes. La biopsia de tejido proporciona el diagnóstico en solo la mitad de los casos. El cultivo confirma el diagnóstico, pero se reportan como positivos en 70 a 80% de los casos. Técnicas de amplificación de ácidos nucleicos, como la reacción en cadena polimerasa (PCR) son otros métodos para el diagnóstico, su mayor ventaja es la rapidez de sus resultados en comparación con el cultivo. Existen muchas modalidades terapéuticas: el tratamiento tópico, la administración sistémica de antimicrobianos, la cirugía, la termoterapia local y la terapia combinada. Sin embargo, los pacientes infectados con M. marinum por lo común, son tratados con antimicrobianos en monoterapia o combinados.

Introduction: Mycobacterium marinum is a type of non-tuberculous mycobacterium (NTM). Infection by this bacterium is frequent in freshwater or saltwater fish and very rarely causes infection in human population. Case report: we present the case of a 60-year-old male patient, who consulted for an ulcerative plaque on the back of his left hand. The histopathological study of biopsy reports: epithelial hyperplasia with a dense infiltrate in dermis and few granulomas with giant cells. Different tests were requested, PCR the only one positive for Mycobacterium marinum, which is why we proceeded to establish an antimicrobial regimen with favorable evolution. Discussion: infection by this bacterium is produced by direct inoculation of the microorganism through wounds or skin erosions or by contaminated fish bites. The forms of clinical presentation vary, being the most common the presence of solitary papules or nodules on fingers or hands. It can also manifest in the form of proximal or sporotrichoid lymphangitis, extension to deep organs, and facial sporotrichoid pattern. Diagnosis requires high index of suspicion, since the frequency of this condition is very low, from 0.04 to 0.27 per 100.000 habitants. Tissue biopsy provides the diagnosis in only half of the cases. Culture confirms the diagnosis, but they are reported as positive in 70 to 80% of cases. Nucleic acid amplification techniques, such as polymerase chain reaction (PCR) are other methods for diagnosis; its greatest advantage is the speed of its results compared to culture. There are many therapeutic modalities: topical treatment, systemic administration of antimicrobials, surgery, local thermotherapy and combination therapy. However, patients infected with M. marinum are usually treated with antimicrobials alone or in combination.

Polimorfismos genéticos asociados a la inmunidad innata y la susceptibilidad genética a la tuberculosis / Genetic polymorphisms associated with innate immunity and to genetic susceptibility to tuberculosis

Resumen La tuberculosis es un problema de salud mundial exacerbado por la ausencia de una vacuna eficaz y la emergencia de cepas multidrogo resistentes. La inmunidad innata, clave en la susceptibilidad a tuberculosis, está asociada a polimorfismos genéticos en TLRs (Toll Like Receptors), VDR (Vitamin D Receptor), INF-γ, TNF-α, entre otros. Recientemente, también a nueve genes causantes de susceptibilidad mendeliana a enfermedades micobacterianas (MSMD), incluyendo genes autosómicos y ligados al cromosoma X. Después de décadas de exitoso manejo, Chile reportó mantención de la mortalidad, aumento en la incidencia de tuberculosis en todas sus formas y casos multidrogo resistentes. La incidencia es mayor en Norte y Centro, donde la Región Metropolitana mostró incremento de población migrante latinoamericana. Consecuentemente, la alta persistencia de la incidencia en tales zonas geográficas, podría asociarse a poblaciones portadoras de polimorfismos de un solo nucleótido (SNP)s y/o MSMD, confiriendo susceptibilidad genética a tuberculosis y/o a BCG diseminada y otros patógenos intramacrofágicos, similar a lo descrito en poblaciones de Europa, Asia, África y América. En conclusión, proponemos considerar la predisposición genética de la población actual, al momento de diseñar políticas nacionales de salud pública para erradicar la tuberculosis.

Tuberculosis is a global health problem exacerbated by the absence of an effective vaccine and emergence of extensive antibiotic-resistant strains. Innate immunity is key to tuberculosis susceptibility, since it is associated with genetic polymorphisms in TLRs (Toll Like Receptors), VDR (Vitamin D Receptor), INF-γ, TNF-α, among others. Recently, also to nine Mendelian Susceptibility Mycobacterial Diseases (MSMD) -causing genes, including autosomal and X-linked genes. After decades of successful management, Chile reported maintenance of mortality and increase in tuberculosis under 15 years and multidrug resistant cases incidence. Moreover, incidence is higher in the North and the Center, where Metropolitan Region showed a sustained increment of the Latin American migrant population. Consequently, the high incidence persistence in such geographic areas could be associated with populations carrying SNPs genetic polymorphisms types and/or MSMD that confer genetic susceptibility to tuberculosis and/or BCG dissemination and other intramacrophagic pathogens, similar to that described in certain populations in Europe, Asia, Africa and America. Corollary, we propose to consider genetic predisposition of the current population, at the time of designing national public health policies to eradicate tuberculosis.

Mycobacterium tuberculosis e micobactérias não tuberculose em paciente com síndrome da imunodeficiência adquirida e câncer: relato de caso / Mycobacterium tuberculosis and non-tuberculous mycobacteria in a patient with acquired immunodeficiency syndrome and cancer: case report

O presente estudo relata o caso de um paciente de difícil tratamento com infecção mista por tuberculose (TB) e micobactérias não tuberculosas (MNT). O paciente é portador de HIV, câncer e outras doenças associadas. A TB foi elucidada em internação devido a quadro de hemoptise. No período da TB/MNT, a carga viral manteve-se indetectável e o Linfócito T CD4+ variou de 117 a 622 cél/mm3. Os principais sintomas foram febre, tosse, emagrecimento e sudorese. O exame de Raio-X mostrou suspeita de TB bilateral cavitária, a baciloscopia foi negativa e várias culturas apresentaram resultado positivo. As identificações dos isolados foram: Complexo Mycobacterium tuberculosis, Mycobacterium intracelullare/chimaera e M. fortuitum, isolados de amostras pulmonares. Iniciado tratamento para TB em outubro de 2015, atualmente tratando de MNT e mantendo cultura positiva com identificação de M. intracelullare. Os Testes de suscetibilidade aos fármacos para M. intracelullare mostraram resistência a Isoniazida, Rifampicina, Ciprofloxacina, Etambutol e Rifabutina. A terapia para a síndrome da imunodeficiência adquirida (AIDS) aumentou a sobrevida do paciente, trazendo novos desafios para o diagnóstico, controle de tratamento e cuidados da atenção básica para os pacientes com TB/micobacterioses/HIV. Este caso exemplifica que a decisão por um tratamento empírico pode ser uma escolha acertada em casos com clínica e imagem compatíveis e baciloscopia ou TRM negativos.

The present study is a case report of a difficult-to-treat patient with mixed tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infection. The patient has HIV, cancer and other associated diseases. TB was elucidated upon hospitalization due to hemoptysis. In the TB/NTM period, the viral load remained undetectable and CD4 ranged from 622 to 117 cells/mm3. The main symptoms were fever, cough, weight loss and sweating. The X-ray examination showed suspicion of bilateral cavitary TB; the bacilloscopy was negative and several cultures presented positive results. The following isolates were identified: Mycobacterium tuberculosis complex, Mycobacterium intracelullare/chimaera and M. fortuitum, isolated from lung samples. The TB treatment was initiated in October 2015, currently treating NTM and maintaining positive culture with identification of M. intracelullare. Antimicrobial sensitivity tests for M. intracelullare showed resistance to Isoniazid, Rifampicin, Ciprofloxacin, Ethambutol and Rifabutin. Acquired Immune Deficiency Syndrome (AIDS) therapy has increased patient survival, bringing new challenges for diagnosis, treatment control, and basic care for TB/mycobacterial/HIV patients. This case exemplifies that the decision of an empirical treatment may be the correct choice in cases with compatible clinical and imaging tests and negative smear microscopy or molecular tests.

Chronic granulomatous inflammation in teleost fish Piaractus mesopotamicus: histopathology model study / Inflamación crónica granulomatosa en el pez teleósteo Piaractus mesopotamicus: modelo de estudio histopatológico

ABSTRACT Objective. This study evaluated the cell kinetic and formation of granuloma during chronic inflammation induced by Bacillus Calmette-Guérin (BCG) in the skeletal muscle of Piaractus mesopotamicus, as a histopathology model to study innate immunity. Materials and methods. Sixty fish were divided in two groups: BCG-inoculated and non-inoculated fish and the inflammatory response analyzed 3, 7, 14, 21 and 33 days post-inoculation (DPI) by histopathology after hematoxylin-eosin and Ziehl-Neelsen staining. Results. 3 DPI of BCG showed a diffuse inflammatory reaction mostly composed by mononuclear cells. The inflammation continued diffuse 7 DPI initiating the cellular organization surrounding the inoculum and have continued at 14 DPI with discrete presence of epithelioid-like type cells with acidophilic cytoplasm and floppy chromatin. Higher cellular organization (21 DPI) surrounding the granuloma with intense peripheral mononuclear inflammatory infiltrate and nevertheless, an increase in the number of fibroblasts and macrophage-like cells was observed. The inflammatory process became less diffuse 33 DPI with formation of small amount of granuloma surrounded by the same type of reaction found in bigger granuloma. Both the young and old granuloma presented typical characteristic around the inoculum composed by a layer of epithelioid-like type cells, besides macrophages, some lymphocytes and abundant fibroblasts. Conclusions. This study showed the feasibility in the use of pacus to study chronic granulomatous inflammatory response induced by BCG, characterized by changes in the kinetics of inflammatory cells in skeletal muscle classifying as immune-epithelioid type, similar to granulomatous inflammation caused by M. marinum in teleost fish.

RESUMEN Objetivo. Este estudio evaluó la cinética celular y la formación de granuloma durante la inflamación crónica inducida por el Bacilo Calmette-Guérin (BCG) en el músculo esquelético de Piaractus mesopotamicus, como modelo histopatológico para estudiar la inmunidad innata. Materiales y métodos. Sesenta peces fueron divididos en dos grupos: peces inoculados con BCG y no inoculados y la respuesta inflamatoria analizada en 3, 7, 14, 21 y 33 días post-inóculo (DPI) por medio del análisis histopatológico y tinciones de hematoxilina-eosina y Ziehl-Neelsen. Resultados. 3 DPI de BCG se observó reacción inflamatoria difusa principalmente formada por infiltrado celular mononuclear. Al 7° DPI la inflamación continuaba difusa con inicio de organización celular alrededor del inoculo, que se observó hasta el 14° DPI con discreta presencia de células de tipo epiteliodes con citoplasma acidófilo y cromatina laxa. Para el 21° DPI se observó alta organización celular alrededor del granuloma con intenso infiltrado mononuclear periférico e incremento en el número de fibroblastos y macrófagos. El proceso inflamatorio se tornó menos difuso a los 33 DPI con formación de pequeños granulomas contenidos dentro de uno más grande. Los granulomas formados más rápidamente así como los formados tardíamente, presentaron características típicas alrededor del inóculo compuesta por una camada de células tipo epitelioides, macrófagos, linfocitos y fibroblastos. Conclusiones. Este estudio mostró la viabilidad del uso del P. mesopotamicus para estudiar la respuesta inflamatoria crónica granulomatosa inducida con BCG, caracterizado por la evolución de la cinética de células inflamatorias en el músculo esquelético clasificándolo como de tipo inmune-epitelioide, similar a la inflamación granulomatosa causada por M. marinum en peces teleósteos.