Relevancia clínica, diversidad y variabilidad genética de distintas especies del género Mycobacterium / Clinical Relevance, Diversity and Genetic Variability of Different Species within the Genus Mycobacterium

Introducción: El término micobacterias no tuberculosas (MNT) incluye distintas especies ambientales capaces de enfermar humanosy/o animales incluso mediante una probable transmisión zoonótica Objetivos. Determinar: la importancia clínica de varias especies del género Mycobacterium y la diversidad genética del Complejo M. avium (MAC), la sensibilidad bacteriana in vitro yel éxito del tratamiento especifico. Materiales y Métodos: Recolección de datos clínicos, epidemiológicos y aislamientos en el periodo 2009-2016; identificación molecular de los aislamientos; determinación de la sensibilidad bacteriana in vitro y de la diversidad genética del MAC; evaluación del tratamiento. Resultados: Fueron diagnosticados 225 casos de micobacteriosis, con prevalencia estable ≈ 6% por año, y 22 especies recuperadas: 4 de rápido desarrollo aisladas de 66 pacientes y 18 de lento desarrollo. MAC fue aislado en 95 casos, 40 M. avium hominissuis, 51 M. intracellulare, 3 M. chimaera, 1 M. colombiense. Se observó mayor probabilidad de enfermar por M. intracellulare en pacientes tratados previamente por tuberculosis (TB). Los pacientes HIV+ tuvieron riesgo incrementado de enfermedad causada por M. avium hominissuis. Los aminoglucósidos, fluoroquinolonas y macrólidos fueron las drogas más activas frente a la mayoría de las MNT. Aproximadamente la mitad de los casos curaron. Conclusiones: M. intracellulare, M. aviumhominissuis con una gran variabilidad genética, y M. abscessus fueron los patógenos más frecuentemente hallados. Un hallazgo importante fue el de casos de enfermedad mixta TB+MNT. Estos pacientes requirieron una terapia con agregado de drogas de segunda línea al esquema terapéutico para TB habiendo curado la mayoría de ellos.

Introduction: The term non-tuberculous mycobacteria (NTM) includes different ambient species capable of sickening humans and/or animals, even by means of a potential zoonotic transmission. Objectives: To determine: The clinical importance of several species within the genus Mycobacterium and the genetic diversity of the M. avium complex (MAC), the in vitro bacterial sensitivity and the success of the specific treatment. Materials and Methods: Collection of clinical and epidemiologic data and information about isolates of the 2009-2016 period; molecular identification of the isolates; determination of the in vitro bacterial sensitivity and genetic diversity of the MAC; treatment evaluation. Results: 225 mycobacteriosis cases were diagnosed, with a stable prevalence of ≈6% per year and 22 recovered species: 4 rapidly growing species isolated from 66 patients and 18 slowly growing species. The MAC was isolated in 95 cases, M. avium hominissuis - 40 cases, M. intracellulare - 51 cases, M. chimaera - 3 cases and M. colombiense - 1 case. We observed a greater probability of getting sick from M. intracellulare in patients previously treated for tuberculosis (TB). HIV-positive patients had a greater risk of falling ill from M. avium hominissuis. Aminoglycosides, fluoroquinolones and macrolides were the most active drugs against most NTM. Approximately half of the cases healed. Conclusions: M. intracellulare, M. aviumhominissuis with great genetic variability and M. abscessus were the most commonly found pathogens. The cases of TB+NTM mixed disease were an important finding. For treating these patients, it was necessary to add second line drugs to the therapeutic regimen for TB; and most of them healed.

Clinical Relevance, Diversity and Genetic Variability of Different Species within the Genus Mycobacterium

Introduction: The term non-tuberculous mycobacteria (NTM) includes different ambient species capable of sickening humans and/or animals, even by means of a potential zoonotic transmission. Objectives: To determine: The clinical importance of several species within the genus Mycobacterium and the genetic diversity of the M. avium complex (MAC), the in vitro bacterial sensitivity and the success of the specific treatment. Materials and Methods: Collection of clinical and epidemiologic data and information about isolates of the 2009-2016 period; molecular identification of the isolates; determination of the in vitro bacterial sensitivity and genetic diversity of the MAC; treatment evaluation. Results: 225 mycobacteriosis cases were diagnosed, with a stable prevalence of ≈6% per year and 22 recovered species: 4 rapidly growing species isolated from 66 patients and 18 slowly growing species. The MAC was isolated in 95 cases, M. avium hominissuis - 40 cases, M. intracellulare - 51 cases, M. chimaera - 3 cases and M. colombiense - 1 case. We observed a greater probability of getting sick from M. intracellulare in patients previously treated for tuberculosis (TB). HIV-positive patients had a greater risk of falling ill from M. avium hominissuis. Aminoglycosides, fluoroquinolones and macrolides were the most active drugs against most NTM. Approximately half of the cases healed. Conclusions: M. intracellulare, M. aviumhominissuis with great genetic variability and M. abscessus were the most commonly found pathogens. The cases of TB+NTM mixed disease were an important finding. For treating these patients, it was necessary to add second line drugs to the therapeutic regimen for TB; and most of them healed

Evolución de la tuberculosis resistente en la Provincia de Buenos Aires en el período 2006 a 2014 / Drug-Resistant Tuberculosis Evolution in Buenos Aires Province During the Period 2016 to 2014

Introducción: En la Argentina la notificación de tuberculosis (TB) mantiene una tendencia descendente, lenta pero sostenida, siendo las formas resistentes las que complican el panorama epidemiológico actual. Objetivo: Describir la incidencia de TB multi y extensivamente resistente (TB M/XDR) en niños y adultos, analizar su transmisión y la relación con los re-tratamientos. Materiales y métodos: En el período 2006-2014 fue notificado un total 41.782 casos totales de TB de los cuales 35.862 (85.8%) eran pulmonares, 24.913 (69,5%) confirmados por bacteriología y, de éstos, 21.842 (87.7%) por examen directo. Un total de 5.712 (13,7%) casos correspondió a menores de 15 años y 35.843 (85,8%) a adultos. Resultados: Fueron registrados 636 casos de TB resistente a los fármacos: 445 (70,0%) con TB MDR, de los cuales 13 (2,9%) fueron niños; 18 (2,6%) casos presentaron TB XDR (2 niños) y 109 (24,5%) eran MDR con resistencia extendida a una fluoroquinolona o un agente inyectable (amicacina, kanamicina, capreomicina, Pre-XDR). Además, 64 casos presentaban mono o poli resistencia. En total 82 (18,4%) pacientes con TB M/XDR cursaban su primer episodio de TB siendo 20 de ellos contactos confirmados de un caso previo de TB. Un total de 19 adultos MDR fueron considerados casos índices de 31 contactos, 13 niños, que desarrollaron la misma forma de TB. Discusión: El contagio desde los casos índices a niños y adultos fue demostrado por epidemiología molecular y clásica. Los genotipos de los aislamientos y la fecha de diagnóstico de la enfermedad permitieron trazar la cadena epidemiológica del contagio.

Introduction: During the last years, Argentina has been maintaining slow but progressive decreasing trends of tuberculosis (TB) incidence rates. In sanitary terms, the drug-resistant forms of the disease are complicating the global control of the disease. Objetive: The main objectives of this study were to describe the incidence of multi and extensive drug-resistant TB (M/XDR) in children and adults, to analyze its transmission within contacts and the relationship with previous treatments. Materials and methods: During 2006-2014 it was notifed to the Control Program of Buenos Aires Province 41,782 TB cases, 5.712 (13.7%) children <15 years old, 35.843 (85.8%) adults; 35,862 (85.8%) patients presented a respiratory form of the disease, 24,913 (69.5%) confrmed by bacteriology, 21,842 (87.7%) by microscopy examination. Results: They were diagnosed 636 cases of drug-resistant TB: 445 (70.0%) MDR TB, 13 (2.9%) children; 18 (2.6%) had a XDR pattern; from 109 (24.5%) individuals the bacteria showed a MDR pattern also resistant to fluoroquinolones or an injectable agent (amikacin, kanamicin or capreomicin). Besides, 64 cases suspected of being MDR were resistant to one or more drugs not accomplishing the MDR criterion. Eighty two (18.4%) patients with M/XDR had their first TB episode being 20 of them, 9 children, contacts of previous TB cases; 19 individuals were considered index cases of another 31 contacts that developed also M/XDR TB. Discussion: Transmission from index cases to contacts was demonstrated by molecular and classical epidemiology. The isolates fngerprinting and the diagnosis of TB dates were useful tools to trace the epidemiologic infection route.

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.