Micobacterias no tuberculosas. ¿Una amenaza emergente? / Non-Tuberculous Mycobacteria. An Emerging Threat?

Introducción y objetivo: Los aislamientos de micobacterias no tuberculosas (MNT) son cada vez más frecuentes. El objetivo principal de nuestro estudio fue conocer el número y la variedad de especies de MNT en nuestra región, su distribución según el origen de la muestra, y la edad y sexo de los pacientes; asimismo, analizar pormenorizadamente los aislamientos clínicamente significativos. Metodología: Estudio prospectivo que incluye todas las MNT aisladas en Asturias durante el período 2005-2012. Las muestras se procesaron siguiendo directrices internacionalmente aceptadas. Para el tratamiento estadístico de los datos se utilizaron tablas de contingencia 2 × 2 aplicando el test exacto de Fisher. Resultados: Se aislaron 3.284 micobacterias: 1.499 Mycobacterium tuberculosis complex (MTB) y 1.785 MNT. A lo largo del estudio se incrementaron los aislamientos de MNT y se redujeron los de MTB. Los aislamientos de MNT fueron más numerosos en hombres que en mujeres (p <0,001). M. gordonae, la especie más frecuentemente aislada, no originó enfermedad en ningún caso. El aislamiento fue clínicamente significativo en 212 pacientes (17,1%), siendo M. kansasii y M. avium las especies que más frecuentemente causaron enfermedad. La diferencia de aislamientos de M. kansasii entre mujeres y hombres fue estadísticamente significativa (p < 0,01). Conclusiones: En nuestro estudio, los aislamientos de MNT se incrementaron un 35%, frente a un descenso del 21% de los casos de MTB. Tanto los aislamientos de MNT como los casos clínicamente significativos fueron más frecuentes en hombres. Solo un 17,1% de las MNT aisladas, principalmente M. avium complex (MAC) y M. kansasii, ocasionaron enfermedad

Introduction and objective: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. Methodology: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2 × 2 contingency tables. Results: A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM. During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P < .001). M. gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M. kansasii and M. avium were most commonly associated with disease. The number of M. kansasii isolates from men was statistically significant (P < .01). Conclusions: In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M. avium complex and M. kansasii

Non-Tuberculous Mycobacteria. An Emerging Threat? / Micobacterias no tuberculosas. ¿Una amenaza emergente?

INTRODUCTION AND OBJECTIVE: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. METHODOLOGY: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2×2 contingency tables. RESULTS: A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM.During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P<.001). M.gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M.kansasii and M.avium were most commonly associated with disease. The number of M.kansasii isolates from men was statistically significant (P<.01). CONCLUSIONS: In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M.avium complex and M.kansasii.

Utilidad de los métodos fenotípicos y genotípicos en el estudio de resistencias de Mycobacterium tuberculosis a fármacos antituberculosos de primera línea / Utility of phenotypic and genotypic testing in the study of Mycobacterium tuberculosis resistance to first-line anti-tuberculosis drugs

Objetivo: Conocer la utilidad de las técnicas moleculares para el diagnóstico de resistencias y la situación de las resistencias a fármacos de primera línea en nuestra área geográfica. Material y método: Desde 2004 a 2013, 1.889 cepas de Mycobacterium tuberculosis complex aisladas en Asturias, España, fueron estudiadas mediante pruebas de sensibilidad fenotípicas (directrices del Clinical and Laboratory Standards Institute) y moleculares (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©). Resultados: Mil setecientas cincuenta y nueve cepas (94,52%) eran sensibles a todos los fármacos de primera línea y 102 cepas (5,48%) presentaban alguna resistencia: 81 cepas (4,35%) a un solo fármaco, 14 (0,75%) con polirresistencia y 7 (0,37%) multirresistentes (resistencia a rifampicina e isoniacida). En total hubo 137 resistencias a fármacos: 60 a isoniacida (3,22%), 7 a rifampicina (0,37%), 9 a pirazinamida (0,48%), 11 a etambutol (0,59%) y 50 a estreptomicina (2,68%). El 75,9% de las mutaciones detectadas (63/83) se correlacionaron con resistencia; mientras que un 24,09% de las mutaciones detectadas (20/83) no implicaban resistencia, correspondiendo 16 a una mutación silente en el codón 514 del gen rpoB. Entre un 0 y un 90% de cepas, dependiendo del fármaco que se considere, eran resistentes aunque no presentaban mutaciones en los genes incluidos en los sistemas comerciales. Conclusiones: Las técnicas moleculares resultan muy útiles sobre todo por la rapidez en la obtención de resultados, aunque estos deben confirmarse con las pruebas de sensibilidad fenotípicas de referencia. La tasa de resistencias a fármacos en nuestra región es baja y los casos de multirresistencia (0,37%) son esporádicos

Objective: To determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region. Material and method: From 2004 to 2013, 1,889 strains of Mycobacterium tuberculosis complex isolated in Asturias, Spain, were studied using phenotypic (Clinical and Laboratory Standards Institute guidelines) and molecular (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©) sensitivity tests. Results: 1,759 strains (94.52%) were sensitive to all first-line drugs, and 102 strains (5.48%) showed some resistance: 81 strains (4.35%) were resistant to 1 single drug, 14 (0.75%) were polyresistant, and 7 (0.37%) were multiresistant (resistant to rifampicin and isoniazid). In total, 137 resistances were identified: 60 to isoniazid (3.22%), 7 to rifampicin (0.37%), 9 to pyrazinamide (0.48%), 11 to ethambutol (0.59%), and 50 to streptomycin (2.68%). Of the mutations detected, 75.9% (63/83) correlated with resistance, while 24.09% of mutations detected (20/83) were not associated with resistance; 16 of these involved a silent mutation at codon 514 of the rpoB gene. Between 0 and 90% of strains, depending on the drug under consideration, were resistant even when no gene mutations were detected using marketed systems. Conclusions: Molecular techniques are very useful, particularly for obtaining rapid results, but these must be confirmed with standard phenotypic sensitivity testing. The rate of resistance in our region is low and multi-drug resistant cases (0.37%) are sporadic

Utility of Phenotypic and Genotypic Testing in the Study of Mycobacterium tuberculosis Resistance to First-Line Anti-Tuberculosis drugs. / Utilidad de los métodos fenotípicos y genotípicos en el estudio de resistencias de Mycobacterium tuberculosis a fármacos antituberculosos de primera línea.

OBJECTIVE: To determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region. MATERIAL AND METHOD: From 2004 to 2013, 1,889 strains of Mycobacterium tuberculosis complex isolated in Asturias, Spain, were studied using phenotypic (Clinical and Laboratory Standards Institute guidelines) and molecular (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©) sensitivity tests. RESULTS: 1,759 strains (94.52%) were sensitive to all first-line drugs, and 102 strains (5.48%) showed some resistance: 81 strains (4.35%) were resistant to 1 single drug, 14 (0.75%) were polyresistant, and 7 (0.37%) were multiresistant (resistant to rifampicin and isoniazid). In total, 137 resistances were identified: 60 to isoniazid (3.22%), 7 to rifampicin (0.37%), 9 to pyrazinamide (0.48%), 11 to ethambutol (0.59%), and 50 to streptomycin (2.68%). Of the mutations detected, 75.9% (63/83) correlated with resistance, while 24.09% of mutations detected (20/83) were not associated with resistance; 16 of these involved a silent mutation at codon 514 of the rpoB gene. Between 0 and 90% of strains, depending on the drug under consideration, were resistant even when no gene mutations were detected using marketed systems. CONCLUSIONS: Molecular techniques are very useful, particularly for obtaining rapid results, but these must be confirmed with standard phenotypic sensitivity testing. The rate of resistance in our region is low and multi-drug resistantcases (0.37%) are sporadic.