Identificación de Mycobacteria no pigmenteda de crecimiento rápido por el Método Molecular de Micobacterium de Genotipo CM / Identification of Fast-Growing Non-Pigmented Mycobacteria by the Genotype® Mycobacterium CM Molecular Method

Introducción: la micobacteria no terberculosa (NTM) forma un grupo heterogéneo de microorganismos que pueden causar infección en humanos. Las micobacterias no pigmentadas de rápido crecimiento (MNPCR) son de interés clínico debido al creciente número de pacientes infectados por ellos y a la dificultad del tratamiento. Dentro de este grupo, Mycobacterium fortuitum, Mycobacterium abscessus y Mycobacterium chelonae son reconocidos como patógenos potenciales; estas especies se han aislado de infecciones pulmonares y extrapulmonares. Objetivo: el objetivo de este trabajo es encontrar la frecuencia de aislamiento de especies micobacterianas de rápido crecimiento, específicamente el complejo Mycobacterium fortuitum, de muestras clínicas utilizando la técnica molecular de diagnóstico GenoType Mycobacterium CM. Material y Método: se analizaron 249 aislados de micobacterias no tuberculosas obtenidas de muestras pulmonares y extrapulmonares de pacientes sintomáticos en el período enero 2018-diciembre de 2022. La técnica molecular GenoType Mycobacterium CM se utilizó para identificar la especie. Resultados: Se obtuvieron 77 (3,9%) aislados de especies no pigmentadas de rápido crecimiento, estas se identificaron en orden decreciente: Mycobacterium fortuitum 65 (84,41%), Mycobacterium abcessus 9 (11,68%) y Mycobacterium chelonae 3 (4%). Conclusiones: los resultados reafirman que el complejo Mycobacterium fortuitum es responsable de la mayoría de las infecciones causadas por la micobacteria en rápido crecimiento en humanos. La técnica diagnóstica GenoType Mycobacterium CM es una herramienta útil para la rápida identificación de micobacterias; proporciona resultados precisos en menos tiempo, acortando significativamente el tiempo diagnóstico, permite la aplicación temprana de tratamiento específico, evitando así la propagación de la infección.

Introduction: non-tuberculous mycobacteria (NTM) form a heterogeneous group of mi-croorganisms that can cause infection in humans. Fast-growing non-pigmented my-cobacteria (MNPCR) are of clinical interest due to the increasing number of patients infected by them and the difficulty of treatment. Within this group, Mycobacterium fortuitum, Mycobacterium abscessus and Mycobacterium chelonae are recognized as potential pathogens; these species have been isolated from both pulmonary and ex-trapulmonary infections. Objective: the objective of this work is to find the frequency of isolation of fast-growing non-pigmented mycobacterial species, specifically the Myco-bacterium fortuitum complex, from clinical samples using the GenoType® Mycobacteri-um CM diagnostic molecular technique. Material and Method: 249 isolates of non-tu-berculous mycobacteria obtained from pulmonary and extrapulmonary samples from symptomatic patients in the period January 2018-December 2022 were analyzed. The G e n oTy p e® Mycobacterium CM molecular technique was used to identify the species. Results: 77 (30.9%) isolates of fast-growing non-pigmented species were obtained, these were identified in decreasing order: Mycobacterium fortuitum 65 (84.41%), Myco-bacterium abcessus 9 (11.68%) and Mycobacterium chelonae 3 (4%). Conclusions: the results reaffirm that the Mycobacterium fortuitum complex is responsible for most in-fections caused by fast-growing mycobacteria in humans. The GenoType® Mycobacte-riumCM diagnostic technique is a useful tool for the rapid identification of mycobacte-ria; it provides accurate results in less time, significantly shortening the diagnostic time, it allows the early application of specific treatment, thus avoiding the spread of infec-tion.

Actualización del manejo de microbacterias no tuberculosas / Update on the management of non-tuberculous mycobacteria

Desde el año 2007 se han generado guías de diagnóstico y tratamiento de micobacterias no tuberculosas (MNTB), la última de las cuales fue desarrollada en el año 2020 por ATS/ERS/ESCMID/IDSA, en ella se actualizan los criterios diagnósticos, los criterios para determinar el inicio de tratamiento y recomendaciones de esquema de antibióticos para las especies más frecuentes. En paralelo se han ido desarrollando terapias alternativas como la fagoterapia. El objetivo de la presente revisión es dar a conocer los cambios que traen estas últimas guías y actualizar algunas de las últimas novedades con respecto al manejo de las micobacterias no tuberculosas.

Since 2007, guidelines for diagnosis and treatment of non-tuberculous Mycobacteria have been generated, the latest of which was developed by ATS/ERS/ESCMID/IDSA, in which the diagnostic criteria, and the criteria for determining the initiation of treatment and antibiotic scheme recommendations for the most frequent species are updated. At the same time, alternative therapies such as phage therapy have been developed. The objective of this review is to show the changes that these latest guidelines bring and update some of the latest developments regarding the management of non-tuberculous Mycobacteria.

Non-tuberculous cutaneous mycobacterioses

Abstract Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.

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.

Identification of nontuberculous mycobacteria species by multiplex real-time PCR with high-resolution melting

Abstract INTRODUCTION: Nontuberculous mycobacteria (NTM) species, as human pathogens, are increasing in the world, as is the difficulty of accurately identifying them. Differential diagnosis, especially between the M. tuberculosis complex and NTM species, and the characterization of NTM species is important. This study aimed to evaluate the performance of a molecular system based on multiplex real-time PCR with high-resolution melting (HRM) for the identification and differentiation of NTM species of clinical importance of an endemic area for tuberculosis in northeastern Brazil. METHODS: The technical protocol of the molecular system was based on multiplex real-time PCR-HRM, and evaluated the sensitivity and specificity of the detection of NTM species in mycobacterial clinical isolates from the studied region. The gold standard method was specific gene sequencing. RESULTS: The sensitivity and specificity of multiplex real-time PCR-HRM modified for differentiation between NTM and M. tuberculosis were 90% and 100%, respectively. The PCR-HRM sensitivities for the characterization of NTM species (M. kansasii, M. abscesses, M. avium, and M. fortuitum) were 94.59%, 80%, 57.14%, and 54%, respectively. CONCLUSIONS The multiplex real-time PCR-HRM modified assay has the potential to rapidly and efficiently identify nontuberculous mycobacteria of clinical importance, which is crucial for immediate implementation of the appropriate therapy and thus avoiding complications and sequelae in patients.

Nontuberculous mycobacteria in patients with suspected tuberculosis and the genetic diversity of Mycobacterium avium in the extreme south of Brazil / Micobactérias não tuberculosas em pacientes com suspeita de tuberculose e a diversidade genética de Mycobacterium avium no extremo sul do Brasil

ABSTRACT Objective: Nontuberculous mycobacteria (NTM) are a heterogeneous group of bacteria that are widely distributed in nature and associated with opportunistic infections in humans. The aims of this study were to identify NTM in patients with suspected tuberculosis who presented positive cultures and to evaluate the genetic diversity of strains identified as Mycobacterium avium. Methods: We studied pulmonary and extrapulmonary samples obtained from 1,248 patients. The samples that tested positive on culture and negative for the M. tuberculosis complex by molecular identification techniques were evaluated by detection of the hsp65 and rpoB genes and sequencing of conserved fragments of these genes. All strains identified as M. avium were genotyped using the eight-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat method. Results: We found that NTM accounted for 25 (7.5%) of the 332 mycobacteria isolated. Of those 25, 18 (72%) were M. avium, 5 (20%) were M. abscessus, 1 (4%) was M. gastri, and 1 (4%) was M. kansasii. The 18 M. avium strains showed high diversity, only two strains being genetically related. Conclusions: These results highlight the need to consider the investigation of NTM in patients with suspected active tuberculosis who present with positive cultures, as well as to evaluate the genetic diversity of M. avium strains.

RESUMO Objetivo: As micobactérias não tuberculosas (MNT) são um grupo heterogêneo de bactérias amplamente distribuídas na natureza e relacionadas com infecções oportunistas em seres humanos. Os objetivos deste estudo foram identificar MNT em pacientes com suspeita de tuberculose e culturas positivas e avaliar a diversidade genética de cepas identificadas como Mycobacterium avium. Métodos: Foram estudadas amostras pulmonares e extrapulmonares provenientes de 1.248 pacientes. As amostras que apresentaram resultado positivo em cultura e negativo para o complexo M. tuberculosis na identificação molecular foram avaliadas por meio da detecção dos genes hsp65 e rpoB e de sequenciamento de fragmentos conservados desses genes. Todas as cepas identificadas como M. avium foram genotipadas pelo método mycobacterial interspersed repetitive unit-variable-number tandem-repeat com oito loci. Resultados: Das 332 micobactérias isoladas, 25 (7,5%) eram MNT. Dessas 25, 18 (72%) eram M. avium, 5 (20%) eram M. abscessus, 1 (4%) era M. gastri e 1 (4%) era M. kansasii. As 18 cepas de M. avium apresentaram alta diversidade, e apenas duas eram geneticamente relacionadas. Conclusões: Esses resultados mostram a necessidade de considerar a investigação de MNT em pacientes com suspeita de tuberculose ativa e culturas positivas e de avaliar a diversidade genética de cepas de M. avium.

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.

Micobacterias no tuberculosas en pacientes con fibrosis quística / Non-tuberculous mycobacteria in cystic fibrosis patients

In recent years there has been a global increase in nontuberculous mycobacteria isolates, especially in patients with cystic fibrosis. As its clinical and radiological characteristics overlap with other infectious agents, diagnostic guidelines were generated based on evidence from patients who do not present cystic fibrosis. A long-term treatment is necessary, involving multiple antibiotics, and the response rate is low. There are variations in the criteria adopted by different centers with regard to lung transplantation in this group of patients.

En los últimos años se ha producido un aumento a nivel mundial del aislamiento de micobacterias no tuberculosas, especialmente en pacientes con fibrosis quística. Como sus características clínicas y radiológicas se superponen con las de otros agentes infecciosos se generaron orientaciones diagnósticas basadas en evidencia de pacientes que no presentan fibrosis quística. El tratamiento es prolongado, involucra múltiples antibióticos y la tasa de respuesta es baja. Existen variaciones en los criterios adoptados por los distintos centros con respecto al trasplante pulmonar en este grupo de pacientes.

Infección por Mycobacterium scrofulaceum en un niño de las Islas Galápagos - Ecuador / Mycobacterium scrofulaceum infection in a pediatric patient from the Galapagos Islands - Ecuador

Resumen Mycobacterium scrofulaceum es una micobacteria atípica de crecimiento lento que tiene como reservorio el ambiente. De forma ocasional causa enfermedad en humanos. Se presenta el caso de un niño de 10 años de edad con fiebre de cuatro meses de evolución, adenopatías cervicales, torácicas, abdominales e inguinales bilaterales, exantema, dolor abdominal y vómitos; con evidencia concomitante de serología positiva para el VEB y cultivo de los ganglios inguinales izquierdos con crecimiento de M. scrofulaceum. Es la primera comunicación de una infección causada por esta micobacteria en Ecuador, y que particularmente se presentó con un patrón de resistencia inusual.

Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.

Cuando la baciloscopía positiva no es tuberculosis. A propósito de un caso y breve review de la literatura / When smear positive is not tuberculosis. About a case and brief review of the literature

El método gold standar para el diagnóstico de la tuberculosis (TB) es el cultivo en medio sólido de Lowenstein-Jensen. Dado el alto costo y los requerimientos de infraestructura y personal entrenado que exige este método, tanto el programa nacional, como las recomendaciones de la Organización Mundial de la Salud (OMS), establecen que una baciloscopía positiva (BAAR +) confirma el diagnóstico de TB. Si bien el cultivo amplía la sensibilidad diagnóstica, tipifica los bacilos, y permite realizar pruebas de sensibilidad, no es un requisito operativo para la definición de confirmación bacteriológica de TB. En Argentina, el 1% de las BAAR (+) corresponden a otras etiologías3. Presentamos un caso comprendido en ese 1%, en el cual mostramos los problemas a los que se enfrenta un paciente (fundamentalmente demora diagnóstica y exposición innecesaria a drogas potencialmente tóxicas) cuando tiene un diagnóstico de TB de acuerdo con los stándares nacionales e internacionales y sin embargo no es TB.

The method gold standard for the diagnosis of tuberculosis (TB) is the culture in Lowenstein-Jensen’s solid way. In view of the high cost and the requirements of infrastructure and trained personnel that demands this method, both the national program, and the recommendations of the World Health Organization (WHO), they establish that a smear-positive confirms TB’s diagnosis. In addition, the culture increases the diagnostic sensitivity, typifies the bacillus and allows the sensitivity tests to be performed, but it is not an operative requirement for the definition of TB’s bacteriological confirmation. In Argentina, 1% of the BAAR (+) are due to other etiologies3. We present a case included in that 1%, in which we show the problems that a patient faces (basically diagnostic delay and unnecessary exposure to potentially toxic drugs) when it has TB’s diagnosis of agreement to the national and international standards and nevertheless it is not TB.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

Micobacterias atípicas en cinco pacientes adultos sin evidencias de inmunosupresión: Construyendo una experiencia / Atypical mycobacterial infections in five adult patients without evidence of immunosuppression: Making an experience

We aim to communicate the experience gathered during the management of infections by atypical mycobacteria in immunocompetent patients in a general practice. Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections were identified: 2 with cutaneous involvement and 3 with lung infection. None of them had evidence of immunosuppression. A patient with elbow bursitis by M. chelonae presented with a high mononuclear count in fluid analysis with mycobacterial growth at the fifth day of culture. He evolved satisfactorily with clarithromycin. A case with M. fortuitum skin infection had a delayed initial diagnosis with progression to local draining lymph nodes; the culture when requested was positive after 13 days of incubation. Patients with pulmonary infection presented with prolonged cough and sputum and had in common to be postmenopausal women displaying small nodules and bronchiectases at lung images, a classical pattern. Time elapsed between respiratory sampling and a definitive inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non-immunosuppresed patients can generate diagnostic and therapeutic challenges. Delay in identification contributes to this problem.

El objetivo de este trabajo es reportar la experiencia acumulada sobre infecciones por micobacterias atípicas en pacientes sin inmunosupresión. Entre el año 2008 y 2013 se observaron cinco pacientes con infección por micobacterias atípicas: dos con infección cutánea y tres con infección pulmonar. Ninguno de estos pacientes tenía evidencias de inmunosupresión. Un paciente con bursitis de codo por M. chelonae tuvo un estudio citoquímico con aumento de celularidad de predominio mononuclear y desarrollo de bacterias al quinto día; respondió favorablemente a claritromicina. Un caso con infección cutánea por M. fortuitum evolucionó en forma prolongada con supuración ganglionar antes del diagnóstico y el cultivo solicitado a los 13 días fue positivo. Los tres pacientes con aislados pulmonares presentaron tos y expectoración y tenían en común ser mujeres en edad post-menopáusica y presentar pequeños infiltrados nodulares asociados a bronquiectasias en el estudio de imágenes pulmonares, un patrón descrito en la literatura científica. En estos tres casos, la latencia entre la toma de muestra y el informe definitivo tuvo un rango de 40 a 89 días. El aislamiento de micobacterias atípicas en muestras de expectoración en pacientes sin inmunosupresión se da en un contexto típico pero plantea dificultades diagnósticas y terapéuticas. El lento crecimiento de estos microorganismos en el laboratorio contribuye a este problema.

Enfermedad por bacilo de Calmette-Guérin (BCG) y deficiencia del receptor β-1 de interleuquina 12: Experiencia clínica de dos casos en una familia y un caso aislado / Bacillus Calmette-Guérin (BCG) disease and interleukin 12 receptor β1 deficiency: Clinical experience of two familial and one sporadic case

BCG disease has been reported in primary and secondary immunodeficiency and as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Investigation of this syndrome has led to the identifications of a series of genetic, inherited defects in the IL-12/IFN-γ axis. MSMD-causing mutations have been found in seven autosomal and two X-linked genes. In these patients, local or disseminated vaccine BCG infections are common. We report a clinical series including two infants with left axillary adenitis ipsilateral to the site of neonatal BCG immunization; one of them member of a family with two previously reported cases and a single sporadic case. All of them were diagnosed sequentially in Puerto Montt, Chile. The aim of this report is to notify the first Chilean disseminated BCG patients without previous immunodeficiency, in whom it was possible to identify an underlying immunodeficiency, although specific tests for IL-12/IFN-γ axis was no performed in our country. Clinical suspicion and international collaboration permitted to confirm IL12-Rβ1 deficiency in 2 of 3 familial cases and a sporadic case.

La enfermedad por el bacilo de Calmette-Guérin (BCG) ha sido reportada en relación a inmunodeficiencias primarias, secundarias y en el síndrome clínico denominado susceptibilidad mendeliana a enfermedades micobacterianas. La investigación de este síndrome ha llevado a la identificación de defectos en el eje interleuquina (IL)- 12/ interferón gamma (IL-12/IFN-γ), habiéndose identificado hasta hoy mutaciones en siete genes autosómicos y dos ligados al cromosoma X. En estos pacientes, las infecciones localizadas o generalizadas por BCG vacunal son comunes. Reportamos una serie clínica constituida por dos lactantes con adenomegalia axilar izquierda recurrente secundaria a vacunación BCG al nacer; uno de ellos integrante de una familia con dos casos reportados previamente y un caso aislado, diagnosticados consecutivamente en Puerto Montt, Chile, con el objetivo de notificar los primeros casos chilenos de diseminación BCG en niños sin inmunodeficiencia previa conocida, en los que se logró identificar la deficiencia inmune subyacente pese a no disponer en el país del estudio específico del eje (IL-12/IFN-γ). La sospecha diagnóstica y colaboración internacional permitieron identificar en dos de los tres casos familiares y en el caso aislado, la deficiencia del receptor β1 de IL 12 (IL12Rβ1).

The Drug Resistance Profile of Mycobacterium abscessus Group Strains from Korea

BACKGROUND: Bacteria of the Mycobacterium abscessus group are the second most common pathogens responsible for lung disease caused by nontuberculous mycobacteria in Korea. There is still a lack of studies investigating the genetic mechanisms involved in M. abscessus resistance to antibiotics other than clarithromycin. This study investigated the characteristics of drug resistance exhibited by M. abscessus clinical isolates from Korea. METHODS: We performed drug susceptibility testing for a total of 404 M. abscessus clinical strains. Subspecies were differentiated by molecular biological methods and examined for mutations in drug resistance-related genes. RESULTS: Of the 404 strains examined, 202 (50.00%), 199 (49.26%), and 3 (0.74%) strains were identified as M. abscessus, M. massiliense, and M. bolletii, respectively. Of the 152 clarithromycin-resistant strains, 6 possessed rrl mutations, while 4 of the 30 amikacin-resistant strains contained rrs mutations, and 5 of the 114 quinolone-resistant strains had gyr mutations. All mutant strains had high minimal inhibitory concentration values for the antibiotics. CONCLUSIONS: Our results showed the distribution of the strains with mutations in drug resistance-related genes was low in the M. abscessus group. Furthermore, we performed drug susceptibility testing and sequence analyses to determine the characteristics of these genes in the M. abscessus group.

Recent Trends in Clinically Significant Nontuberculous Mycobacteria Isolates at a Korean General Hospital

Lung disease caused by nontuberculous mycobacteria (NTM) represents an increasing proportion of all mycobacterial diseases. We investigated recent occurrences of NTM and evaluated the clinical significance of NTM isolates from 752 respiratory specimens collected from patients at National Health Insurance Service Ilsan Hospital between January 2007 and May 2011. Specimens were incubated on solid and liquid media (BACTEC MGIT 960, BD, USA) for 6-8 weeks, and PCR and reverse blot hybridization were performed (REBA Myco-ID, Molecules & Diagnostics, Korea). Clinical features of the patients were reviewed through medical records. The most frequently isolated organism was Mycobacterium avium (46.7%), followed by M. intracellulare (14.8%), M. fortuitum (7.2%), and M. abscessus (6.6%). The most common mycobacteria among definitive cases of NTM lung disease were M. avium (42/351, 12.0%), M. intracellulare (19/111, 17.1%), M. abscessus (11/50, 22.0%), M. massiliense (4/13, 30.8%), and M. fortuitum (4/54, 7.4%). Clinically significant cases of NTM lung disease increased from 4 patients in 2007 to 32 in 2011. The mean patient age was 64 yr (range: 35-88 yr), and 58 (64%) patients were women. Patients suffered from cough, productive sputum, and hemoptysis. In summary, the most common mycobacteria causing NTM lung disease were M. avium and M. intracellulare; however, cases of M. massiliense and M. abscessus infection are on the rise in Korea.

Mycobacterium aurum keratitis: an unusual etiology of a sight-threatening infection

Atypical fast-growing Mycobacterium species are usually identified after laser-assisted in situ keratomileusis, cosmetic surgeries, and catheter-related, pulmonary or soft tissue infections. We herein present the case of a 56-year-old man with purulent discharge, redness, and foreign body sensation in his left eye. He underwent two surgeries that partially controlled the infection but were not curative. Corneal transplantation was performed, and a biopsy of the excised cornea indicated Mycobacterium aurum infection, which was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis. This appears to be the first documented case of keratitis attributable to the non-tuberculous mycobateria M. aurum. The intractable extra-ocular progression of the disease in the absence of general signs or symptoms was notable. We suggest considering non-tuberculous mycobacteria among the probable causes of complicated keratitis or keratitis that does not respond to drug treatment, especially in regions where tuberculosis is endemic.

Disease caused by non-tuberculous mycobacteria: diagnostic procedures and treatment evaluation in the North of Buenos Aires Province

Non-tuberculous mycobacteria (NTM) have emerged as pathogens frequently associated to HIV co-infection. The aims of this study were to describe the clinical importance of NTM in patients from the North of Buenos Aires Province and the drug-susceptibility patterns in relation with the therapy used. A total of 23,624 clinical specimens were investigated during the period 2004-2010. Ziehl-Neelsen stain and cultures were used for diagnosis. Molecular and biochemical tests were performed to identify the mycobacteria. TB and mycobacterioses cases were 2 118 and 108 respectively. Sixteen NTM species were found: Mycobacterium avium and Mycobacterium intracellulare as the main causative agents. Infections produced by more than one species at the same time were confirmed (4 cases). Macrolides and fluoroquinolones were the most active in vitro drugs. Treatment evaluation showed that 68.0 % of the cases completed the therapy, 20 % died; and 12 % were relapses. The cases in which the treatment outcome was evaluated received an individual tailor-made therapeutic scheme including those drugs showing in vitro activity and presumed in vivo usefulness. More than a quarter of the patients had HIV co-infection and the majority of the deaths were associated with this co-infection.

Enfermedad causada por micobacterias no tuberculosas: diagnóstico y evaluación del tratamiento en el norte del Gran Buenos Aires. Las micobacterias no tuberculosas (MNT) emergieron como patógenos frecuentemente asociados a la co-infección con el HIV. EL objetivo del estudio fue describir la importancia clínica de las MNT en pacientes de la región norte de la provincia de Buenos Aires y los patrones de drogo-sensibilidad en relación con la terapia empleada. Se investigó un total de 23.624 especímenes clínicos durante, el período 2004-2010. La tinción de Ziehl-Neelsen y los cultivos se utilizaron para diagnóstico. Las micobacterias fueron identificadas mediante pruebas bioquímicas y moleculares. Los casos de tuberculosis y micobacteriosis fueron 2 118 y 108, respectivamente. Se encontraron 16 especies de MNT, siendo las principales, Mycobacterium avium y Mycobacterium intracellulare. En 4 casos se confirmaron infecciones producidas por más de una especie al mismo tiempo. Los macrólidos y las fluoroquinolonas tuvieron mayor actividad in vitro. La evaluación del tratamiento confirmó que el 68 % de los casos completó la terapia; 20 % murió y el 12 % recayó. Los casos en los que se evaluó el tratamiento recibieron un esquema terapéutico individual incluyendo aquellas drogas que mostraron actividad in vitro. Más de un cuarto de los pacientes tuvieron co-infeccion con el HIV y la mayoría de las muertes estuvieron asociadas con esta co-infección.

Mycobacterial Pulmonary Infections in Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.