[M. tuberculosis complex drug resistance in Navarre: differences between the local and immigrant populations]. / Resistencias de M. tuberculosis complex en Navarra: diferencias entre población autóctona e inmigrante (2000-2007).

BACKGROUND: Tuberculosis is an important public health problem, whose epidemiology in our country has changed in recent years due to the increase in the immigrant population. The aim of this article is to evaluate the frequency of resistance to the four principal antitubercular drugs in both the local and immigrant populations. METHODS: A study was made of the antibiograms of 457 isolations of Mycobacterium tuberculosis carried out in the Hospital of Navarre in 2000-2007. The antibiograms were processed using the BACTEC460TB system. RESULTS: Twenty six point three percent of the strains corresponded to immigrants, with a significant increase occurring over the period. The frequencies of resistances to the different antitubercular drugs in the local and immigrant populations respectively were: to at least one 5.6% vs 20.8% (p <0.001); to isoniazid 4.5% vs 14.2% (p <0.001); to streptomycin 2.4% vs 12.6% (p <0.001); to rifampicin 0.9% vs 5% (p <0.05); to ethambutol 0.3% vs 2.5% (p <0.05); and multiresistance 0.3% vs 2.5% (p <0.05). CONCLUSION: There are significant differences between local and immigrant populations in the pattern of resistances of the strains isolated. The immigrant population, due to the high frequency with which resistance is shown to isoniazid, must be treated initially with a pattern of four drugs until the result of the biogram is available.

Resistencias de M. tuberculosis complex en Navarra: diferencias entre población autóctona e inmigrante (2000-2007) / M. tuberculosis complex drug resistance in Navarre: differences between the local and immigrant populations

Fundamento. La tuberculosis es un importante problemade salud pública, cuya epidemiología ha cambiadoen los últimos años en nuestro país debido al aumentode población inmigrante. El objetivo de este trabajo hasido valorar la frecuencia de resistencias a los cuatroantituberculosos principales, tanto en población autóctonacomo inmigrante.Material y métodos. Se han estudiado los antibiogramasde 457 aislamientos de Mycobacterium tuberculosisrealizados en el Hospital de Navarra en el periodo 2000-2007. Los antibiogramas fueron procesados mediante elsistema BACTEC460TB.Resultados. El 26,3% de las cepas correspondieron a inmigrantes,produciéndose a lo largo del periodo un incrementosignificativo. Las frecuencias de resistenciasa los distintos fármacos antituberculosos en poblaciónautóctona e inmigrante, respectivamente fueron: a almenos uno 5,6% vs 20,8% (p <0,001), a isoniacida 4,5%vs 14,2% (p <0,001), a estreptomicina 2,4% vs 12,5% (p<0,001), a rifampicina 0,9% vs 5% (p <0,05), a etambutol0,3% vs 2,5% (p <0,05) y multirresistencia 0,3% vs 2,5%(p <0,05).Conclusión. Existen diferencias significativas entre lapoblación autóctona e inmigrante en el patrón de resistenciasde las cepas aisladas. Esta última, debidoa la alta frecuencia con que presenta resistencia a laisoniacida, debe tratarse inicialmente con una pautade cuatro fármacos hasta disponer del resultado del antibiograma(AU)

Background. Tuberculosis is an important publichealth problem, whose epidemiology in our countryhas changed in recent years due to the increase in theimmigrant population. The aim of this article is to evaluatethe frequency of resistance to the four principalantitubercular drugs in both the local and immigrantpopulations.Methods. A study was made of the antibiograms of 457isolations of Mycobacterium tuberculosis carried out inthe Hospital of Navarre in 2000-2007. The antibiogramswere processed using the BACTEC460TB system.Results. Twenty six point three percent of the strainscorresponded to immigrants, with a significant increaseoccurring over the period. The frequencies of resistancesto the different antitubercular drugs in the local andimmigrant populations respectively were: to at leastone 5.6% vs 20.8% (p <0.001); to isoniazid 4.5% vs 14.2%(p <0.001); to streptomycin 2.4% vs 12.5% (p <0.001);to rifampicin 0.9% vs 5% (p <0.05); to ethambutol 0.3%vs 2.5% (p <0.05); and multiresistance 0.3% vs 2.5% (p<0.05).Conclusion. There are significant differences betweenlocal and immigrant populations in the pattern of resistancesof the strains isolated. The immigrant population,due to the high frequency with which resistanceis shown to isoniazid, must be treated initially with apattern of four drugs until the result of the biogram is available(AU)

[Clinical relevance of nontuberculous mycobacteria]. / Relevancia clínica de los aislamientos de micobacterias no tuberculosas.

BACKGROUND: The isolation of nontuberculous mycobacteria (NTM) has increased in recent years largely due to the use of liquid cultivation media. In many cases such isolations lack clinical relevance, which is why the evaluation of their meaning must be carried out on the basis of international clinical criteria. This article studies the impact of using the criteria that the American Thoracic Society (ATS) has established for differentiating an infection of NTM colonisation in respiratory samples. METHODS: Microbiological and clinical study of the patients with repeated isolations of NTM in respiratory samples registered in our laboratory between 2000 and 2004. RESULTS: One hundred and sixteen positive cultivations of NTM were obtained, repeatedly isolated in 46 episodes corresponding to 42 patients. Eleven different species were identified: M. xenopi (16 cases), M. avium (12), M. kansasii (7), M. fortuitum (5), M. malmoense (2) and, finally, 1 of each of the following: M. genavense, M. simiae, M. gordonae and M. lentiflavum. It was possible to study 36 patients, of whom 17 met the criteria of the ATS, and, out of these, only 12 received specific treatment. In those cases that did not meet the ATS criteria the isolations did not have any clinical repercussion. In both the treated and untreated groups a clearly differentiated evolution was not observed. CONCLUSIONS: Facing the difficulty of attributing an etiological role to an NTM of respiratory samples, it is necessary to follow international criteria such as those of the ATS before beginning a specific treatment in order to avoid the incorrect treatment of patients.

Relevancia clínica de los aislamientos de micobacterias no tuberculosas / Clinical relevance of nontuberculous Mycobacteria

Fundamento: El aislamiento de micobacterias no tuberculosas (MNT) se ha incrementado en los últimos años debido en gran parte a la utilización de medios de cultivo líquidos. Estos aislamientos carecen en muchos casos de relevancia clínica, por lo que la valoración de su significado debe realizarse en base a unos criterios clínicos internacionales. En el presente trabajo hemos estudiado el impacto que supondría la aplicación de los criterios que la American Thoracic Society (ATS) ha establecido para diferenciar en muestras respiratorias una infección de una colonización por MNT. Métodos: Estudio microbiológico y clínico de los pacientes con aislamientos repetidos de MNT en muestras respiratorias registrados en nuestro laboratorio entre los años 2000-2004. Resultados: Se obtuvieron 116 cultivos positivos de MNT aisladas repetidamente en 46 episodios correspondientes a 42 pacientes. Se identificaron 11especies distintas: M. xenopi (16 casos), M. avium (12), M. kansasii (7), M. fortuitum (5), M. malmoense (2) y finalmente 1 de cada una de las siguientes: M. genavense, M. simiae, M. gordonae y M. lentiflavum. Se pudieron estudiar 36 pacientes, de los que 17 cumplían los criterios de la ATS y, de estos, sólo 12 recibieron tratamiento específico. En los casos que no se cumplían los criterios de la ATS los aislamientos no tuvieron ninguna repercusión clínica. En ambos grupos, tratados y no tratados, no se observó una evolución claramente diferenciada. Conclusiones: Ante la dificultad de atribuir a una MNT de muestras respiratorias un papel etiológico, es necesario atenerse a criterios internacionales como los de la ATS antes de iniciar un tratamiento específico para evitar tratamientos incorrectos a los pacientes (AU)

Background: The isolation of non tuberculous mycobacterias (NTM) has increased in recent years largely due to the use of liquid cultivation media. In many cases such isolations lack clinical relevance, which is why the evaluation of their meaning must be carried out on the basis of international clinical criteria. This article studies the impact of using the criteria that the American Thoracic Society (ATS) has established for differentiating an infection of NTM colonization in respiratory samples. Methods: Microbiological and clinical study of the patients with repeated isolations of NTM in respiratory samples registered in our laboratory between 2000and 2004.Results. One hundred and sixteen positive cultivations of NTM were obtained, repeatedly isolated in 46episodes corresponding to 42 patients. Eleven different species were identified: M. xenopi (16 cases), M.avium (12), M. kansasii (7), M. fortuitum (5), M. malmoense (2) and, finally, 1 of each of the following: M. genavense, M. simiae, M. gordonae and M. lentiflavum. It was possible to study 36 patients, of whom 17 met the criteria of the ATS, and, out of these, only 12 received specific treatment. In those cases that did not meet the ATS criteria the isolations did not have any clinical repercussion. In both the treated and untreated groups a clearly differentiated evolution was not observed. Conclusions: Facing the difficulty of attributing an etiological role to an NTM of respiratory samples, it is necessary to follow international criteria such as those of the ATS before beginning a specific treatment in order to avoid the incorrect treatment of patients (AU)

Valoración de la prueba de amplificación MTD-2 para la detección directa de Mycobacterium tuberculosis en la muestra / Evaluation of the MTD-2 test for the direct detection of Mycobacterium tuberculosis in specimens

Fundamento. Valorar la rentabilidad de la prueba Amplified Mycobacterium Tuberculosis DirecVt Test (MTD-2, Gen-Probe) en el diagnóstico microbiológico de la tuberculosis.Métodos. Se valoraron los resultados obtenidos con la prueba MTD-2 realizada en 146 muestras, junto con los del cultivo y baciloscopia. MTD-2 se realizó en todas las muestras con baciloscopia positiva (n=47) y en muestras con baciloscopia negativa, si había sido solicitada por el clínico (n=19); además, se testaron una serie de muestras seleccionadas en el laboratorio en base a los datos clínicos y a la calidad de la muestra (n=80). Se consideraron casos de tuberculosis aquellos en los que se aisló Mycobacterium tuberculosis y los que fueron tratados como tales.Resultados. Los resultados de sensibilidad, especificidad, valor predictivo positivo y negativo de la MTD-2 fueron: 95, 76, 71 y 96%. Para el cultivo: 84, 100, 100, y 90% y para la baciloscopia: 75, 94, 89 y 86% respectivamente. En las muestras con baciloscopia positiva, MTD-2 mostró una alta especificidad, diferenciando las que correspondían a M. tuberculosis de las debidas a otras micobacterias. En las muestras con baciloscopia negativa, la sensibilidad no alcanzó los niveles deseados y se obtuvo un bajo valor predictivo positivo. Conclusiones. MTD-2 ha demostrado ser de gran utilidad en muestras con baciloscopia positiva pues en pocas horas permite diagnosticar una tuberculosis o excluirla. Sin embargo, no nos parece recomendable su empleo en el diagnóstico rutinario de la tuberculosis, debido a su bajo valor predictivo positivo. Por esto, siempre que sea positiva en una muestra con baciloscopia negativa, éste resultado debe ser confirmado con otra muestra

Background. To evaluate the utility of the Amplified Mycobacterium Tuberculosis Direct Test (MTD-2, Gen-Probe) in the microbiological diagnosis of tuberculosis.Methods. We evaluated the results obtained in 146 specimens with the MTD-2 test, together with those of the culture and smears. The MTD-2 test was performed on all the smear positives specimens (n=47), on the smear-negative specimens, when the test was demanded (n=19), and in other smear-negative specimens previously selected, according to the clinical history of the patient (n=80). We considered real cases of tuberculosis, those that were culture positive for Mycobacterium tuberculosis and those that were specifically treated.Results. The overall sensitivity, specificity, positive and negative predictive values for the MTD test were: 95, 76, 71, and 96%, for the culture; and 84, 100, 100 and 90% and 75, 94, 89 and 86% for the smears, respectively. In smear positive specimens, the test showed a great specificity, and differentiated M. tuberculosis from other mycobacteria. In the smear negatives, the sensitivity of the test was low and so was the positive predictive value, especially in series performed with a high work load.Conclusions. Data from our study show that the MTD-2 test is a reliable method for rapid diagnosis of tuberculosis in smear positive specimens. However, due to its low sensitivity and positive predictive value, it is not recommended in the routine diagnosis of tuberculosis. Also, for this reason, whenever a positive result is obtained with a smear negative specimen, the result needs to be confirmed with another specimen

[Study of the resistance of Mycobacterium tuberculosis to the principal tuberculostatics (Hospital of Navarra 1996-2003)]. / Estudio de la resistencia de Mycobacterium tuberculosis a los principales tuberculostáticos (Hospital de Navarra 1996-2003).

INTRODUCTION: The aim of this study was to evaluate the sensitivity to the principal tuberculostatics of the M. tuberculosis stocks isolated in our laboratory and to study the factors related to resistance. METHODS: Study of 475 stocks of M. tuberculosis corresponding to all cases diagnosed in the eight year period between 1996 and 2003. We employed the BACTEC 460TB system, together with Lowenstein solid medium, in the cultivation of the samples. The sensitivity studies were carried out using the BACTEC 460TB system. RESULTS AND CONCLUSIONS: Both the incidence and the number of cases of resistant tuberculosis showed oscillations over the eight years of the study. The fact that there is no homogeneous tendency makes it necessary to maintain active surveillance of this process. Global resistance to isoniacide was 8%, making it is convenient to carry out sensitivity studies in all the diagnosed cases. The cases of multiresistant tuberculosis (resistant to at least isoniacide and rifampicin), did not exceed 3%. The prognosis of the patients with resistant tuberculosis was bleak in cases of coinfection with HIV; however, when the immunological defences were conserved, and guidelines for treatment with active drugs were provided, the recovery of the majority of the patients was achieved. At present, sensitive and rapid procedures are available to us, making it recommendable to study the sensitivity of all the stocks of M. tuberculosis that are isolated; this is essential in the case of HIV positive or immigrant patients.

Estudio de la resistencia de Mycobacterium tuberculosis a los principales tuberculostáticos (Hospital de Navarra 1996-2003) / Study of the resistance of Mycobacterium tuberculosis to the principal tuberculostatics (Hospital of Navarra 1996-2003)

Introducción. El objeto de este trabajo ha sidovalorar la sensibilidad a los principales tuberculostáticosde las cepas de M. tuberculosis aisladas en nuestrolaboratorio y estudiar los factores relacionados con laresistencia.Material y métodos. Se han estudiado 475 cepasde M. tuberculosis correspondientes a la totalidad delos casos diagnosticados entre los años 1996-2003ambos inclusive.En el cultivo de las muestras, se utilizó el sistemaBACTEC 460TB, junto con el medio sólido de Lowenstein.Los estudios de sensibilidad se realizaron medianteel sistema BACTEC 460TB.Resultados y conclusiones. Tanto la incidencia,como el número de casos de tuberculosis resistentes,se presentaron con oscilaciones a lo largo de los 8 añosdel estudio. El hecho de que no exista una tendenciahomogénea, obliga a mantener una vigilancia activafrente a este proceso.La resistencia global a isoniacida fue del 8%, por loque es conveniente realizar estudios de sensibilidad entodos los casos diagnosticados.Los casos de tuberculosis multirresistentes (resistentesal menos a isoniacida y rifampicina), no superaronel 3%.El pronóstico de los pacientes con tuberculosisresistente fue sombrío en los casos de coinfección conel VIH, sin embargo, cuando las defensas inmunológicasestaban conservadas, y se pautó un tratamientocon drogas activas, se consiguió la recuperación de lamayoría de los pacientes.En la actualidad, disponemos de procedimientossensibles y rápidos que hacen recomendable el estudiode sensibilidad en todas las cepas de M. tuberculosisaisladas, y en el caso de pacientes VIH+ o inmigrantes,resulta imprescindible

Introduction. The aim of this study was toevaluate the sensitivity to the principaltuberculostatics of the M. tuberculosis stocks isolatedin our laboratory and to study the factors related toresistance.Methods. Study of 475 stocks of M. tuberculosiscorresponding to all cases diagnosed in the eight yearperiod between 1996 and 2003.We employed the BACTEC 460TB system, togetherwith Lowenstein solid medium, in the cultivation of thesamples. The sensitivity studies were carried out usingthe BACTEC 460TB system.Results and conclusions. Both the incidence andthe number of cases of resistant tuberculosis showedoscillations over the eight years of the study. The factthat there is no homogeneous tendency makes itnecessary to maintain active surveillance of thisprocess.Global resistance to isoniacide was 8%, making itis convenient to carry out sensitivity studies in all thediagnosed cases.The cases of multiresistant tuberculosis (resistantto at least isoniacide and rifampicin), did not exceed3%.The prognosis of the patients with resistanttuberculosis was bleak in cases of coinfection with HIV;however, when the immunological defences wereconserved, and guidelines for treatment with activedrugs were provided, the recovery of the majority ofthe patients was achieved.At present, sensitive and rapid procedures areavailable to us, making it recommendable to study thesensitivity of all the stocks of M. tuberculosis that areisolated; this is essential in the case of HIV positive orimmigrant patients

[Evaluation of the MTD-2 test for the direct detection of Mycobacterium tuberculosis in specimens]. / Valoración de la prueba de amplificación MTD-2 para la detección directa de Mycobacterium tuberculosis en la muestra.

BACKGROUND: To evaluate the utility of the Amplified Mycobacterium Tuberculosis Direct Test (MTD-2, Gen-Probe) in the microbiological diagnosis of tuberculosis. METHODS: We evaluated the results obtained in 146 specimens with the MTD-2 test, together with those of the culture and smears. The MTD-2 test was performed on all the smear positives specimens (n=47), on the smear-negative specimens, when the test was demanded (n=19), and in other smear-negative specimens previously selected, according to the clinical history of the patient (n=80). We considered real cases of tuberculosis, those that were culture positive for Mycobacterium tuberculosis and those that were specifically treated. RESULTS: The overall sensitivity, specificity, positive and negative predictive values for the MTD test were: 95, 76, 71, and 96%, for the culture; and 84, 100, 100 and 90% and 75, 94, 89 and 86% for the smears, respectively. In smear positive specimens, the test showed a great specificity, and differentiated M. tuberculosis from other mycobacteria. In the smear negatives, the sensitivity of the test was low and so was the positive predictive value, especially in series performed with a high work load. CONCLUSIONS: Data from our study show that the MTD-2 test is a reliable method for rapid diagnosis of tuberculosis in smear positive specimens. However, due to its low sensitivity and positive predictive value, it is not recommended in the routine diagnosis of tuberculosis. Also, for this reason, whenever a positive result is obtained with a smear negative specimen, the result needs to be confirmed with another specimen.

[Effect of the number of samples studied on the diagnosis of tuberculosis]. / Influencia del número de muestras estudiadas en el diagnóstico de la tuberculosis.

BACKGROUND: For the microbiological diagnosis of tuberculosis, most standard laboratory guidelines recommend the processing of multiple specimens. This fact added to the nonspecific clinical presentation of many cases, contribute to a low efficiency of the tuberculosis laboratory. The introduction of new procedures have increased the sensibility of the diagnosis and so the cost. The object of our work, was to asses the value of examining 3-6 specimens, in optimizing the diagnosis. METHODS: We retrospectively reviewed 327 specimens from 105 patients with culture-proven tuberculosis, between 1997-1998. All specimens were received in the laboratory within 1 month of the initial diagnosis. RESULTS: Of the 7694 specimens received for acid-fast smear and culture in that period of time, 519 (6.7%) were positive for mycobacteria, many of them without clinical relevance. The average number of specimens processed by patient was 3.1, however 22% of the patients with culture-proven tuberculosis had less than tree specimens submitted at the time of diagnosis and 19% had more than three. In 49.5% of the patients, all the smears were negative and the diagnosis was done by culture. With the first specimen submitted were diagnosed 76% of the patients, and with the second we reach 94.2%, finally, we needed 3 specimens for the diagnosis of 104 from the 105 cases (99%). CONCLUSIONS: With the better sensibility achieved in the detection procedures, the interest in the improvement of the efficiency in the tuberculosis laboratory should consider the contribution of the specimen number on the diagnosis. If studying only one specimen we could fail 25% of the early diagnosis, we have rarely found more than two specimens being of diagnostic value. As the time for detecting a positive culture has decrease with the use of liquid media and probes for identification, we would recommend to submit only two specimens for the routine diagnosis and see the patient again 1 moth later. If in this time, the laboratory has'nt obtain any positive result and the clinician still suspect a tuberculosis, a second set of specimens can be submitted. With this measures, laboratory that received a great number of specimens, could assume the work of small laboratory without increasing there work and budget, and the diagnosis of tuberculosis will be optimized.