Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

Factores asociados a tuberculosis pre extensamente resistente en pacientes del Hospital Nacional Dos de Mayo, Lima, Perú / Factors associated with pre-extensively drug-resistant tuberculosis in patients at Dos de Mayo National Hospital, Lima - Perú

INTRODUCCIÓN: La resistencia a fármacos antituberculosos está influenciada por las características personales y las condiciones de salud de países en vías de desarrollo. OBJETIVO: Determinar los factores asociados a TB-pre extensamente resistente (TB-PRE XDR) en pacientes del Hospital Nacional Dos de Mayo (HNDM) entre 2017 y 2019. PACIENTES Y MÉTODO: Se desarrolló un estudio caso control no pareado, definiendo como caso al paciente con TB- PRE XDR y como control al paciente con TB-S. Se recolectaron variables epidemiológicas, clínicas y radiológicas. RESULTADOS: Se analizaron 51 casos y 102 controles. El análisis bivariado determinó como factores con p 51 años (OR: 0,17, IC95%: 0,05-0,51), uso de drogas (OR:2,5, IC95%: 1,1-5,4), antecedente de TB (OR: 20, IC95%: 8,4-47), reclusión previa (OR: 8, IC95%: 2,7-23,8), infección por VIH (OR: 0,2, IC95%: 0,08-1) y uso previo de fármacos antituberculosos (OR: 21, IC95%: 8,8-50). El análisis de regresión logística identificó como factores asociados a TB-PRE XDR al contacto de TB, antecedente de TB, tiempo de enfermedad y uso previo de fármacos antituberculosos. CONCLUSIÓN: Las medidas para limitar el desarrollo de TB-PRE XDR en pacientes con TB-S deben incidir sobre el antecedente de TB, contacto con TB, tiempo de enfermedad y uso previo de anti-TB no controlados; sin embargo, existen resultados no concluyentes sobre el hábito nocivo y la comorbilidad, siendo necesario más estudios para determinar su influencia como factores asociados identificables.

BACKGROUND: Resistance to anti-TB drugs is influenced by personal characteristics and health conditions in developing countries. AIM: To determine the factors associated with pre-extensively drug-resistant tuberculosis (PRE XDR-TB) at Hospital Nacional Dos de Mayo (HNDM) in patients between the 2017 and 2019. METHODS: An unpaired case control study was developed; defining as case PRE XDR-TB patient and as control S-TB patient. Epidemiological, clinical and radiological variables were collected. RESULTS: We analyzed 51 cases and 102 controls. The bivariate analysis showed as factors with p 51 years (OR: 0.17, 95% CI: 0.05-0.51), drug use (OR: 2.5, 95% CI: 1.1-5.4), previous history of TB (OR: 20, 95% CI: 8.4-47), previous confinement (OR: 8, 95% CI: 2.7-23.8), HIV infection (OR: 0.2, 95% CI: 0.08-1) and previous use of antiTB drugs (OR: 21, 95% CI: 8.8-50). The logistic regression analysis identified as associated factors with PRE XDR-TB the previous contact with TB, a history of TB, length of illness and previous use of tuberculosis antibiotics. CONCLUSION: The measures to limit the development of TB-PRE XDR in patients with TB-S must include the previous history of TB, TB contact, length of illness and previous use of uncontrolled antibiotics against TB; however, there are inconclusive results about the harmful habits and comorbidity, requiring more studies to determine their influence as identifiable associated factors.

Factores de riesgo asociados a la farmacorresistencia y al tratamiento no exitoso de la tuberculosis en Chile 2014-2018 / Risk factors and predictors of drug resistance in tuberculosis: A comprehensive analysis of cases in Chile (2014-2018)

OBJETIVOS: Determinar los factores de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso de tuberculosis en Chile durante el 20142018. METODOLOGÍA: Estudio transversal observacional analítico que incluye los pacientes notificados con tuberculosis (TB) que ingresaron a tratamiento durante el 2014-2018 en Chile, contenidos en el registro nacional TB. Se determinaron variables demográficas, clínicas y grupos de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso en pacientes con TB mediante regresión logística. RESULTADOS: Entre los años 2014-2018 se notificaron 13.1761 pacientes con TB en Chile, de los cuales 3,4% (n = 445) son farmacorresistentes. El 43,1% de estos son TB resistente a rifampicina (TB-RR), multidrogorresistente (TB-MDR) y extensamente resistente (TB-XDR). Los factores de riesgo que generaron mayor probabilidad de presentar farmacorresistencia fueron la recaída (OR: 4,27; IC 95% 2,94; 6,20), extranjero (OR: 3,97; IC 95% 2,86; 5,52), TB pulmonar (OR: 2,92; IC 95% 1,71; 4,99) y VIH (OR: 1,97; IC 95% 1,33; 2,90). Frente a la probabilidad de generar un tratamiento no exitoso, las variables que presentaron mayor probabilidad fueron situación de calle (OR: 3,33; IC 95% 2,45; 4,52), drogadicción (OR: 1,91; IC 95% 1,52; 2,41), extranjero (OR: 1,51; IC: 95% 1,25; 1,83), farmacorresistencia (OR: 2,81; IC 95% 1,87; 4,20), VIH (OR: 3,24; IC: 95% 2,61; 4,02), no pertenecer a un pueblo indígena (OR: 1,43; IC: 95% 1,00; 2,06) alcoholismo (OR: 1,25; IC 95% 1,01; 1,54), TB pulmonar (OR: 1,43; IC 95% 1,20; 1,70) y sexo masculino (OR: 1,44; IC 95% 1,25; 1,65). CONCLUSIONES: Los factores de riesgo identificados como la recaída y la coinfección con VIH como predictores de farmacorresistencia destaca la complejidad del manejo de la enfermedad. Asimismo, la presencia de situaciones de calle, drogadicción y alcoholismo resalta la necesidad de enfoques específicos y personalizados para abordar la tuberculosis en distintos grupos poblacionales. Estos resultados subrayan la importancia de abordar estos factores de riesgo en la gestión y tratamiento de la tuberculosis en Chile, sugiriendo la necesidad de estrategias específicas y personalizadas.

OBJECTIVE: Determine the risk factors associated with drug resistance and unsuccessful treatment of tuberculosis in Chile between 2014 and 2018. METHODOLOGY: Analytical observational cross-sectional study including patients diagnosed with Tuberculosis (TB) who entered treatment during 2014-2018, contained in the national TB records. Demographic, clinical variables, and risk groups associated with drug resistance and unsuccessful treatment in TB patients were determined using logistic regression. RESULTS: Between 2014 and 2018, 13,1761 TB patients were reported in Chile, of whom 3.4% (n = 445) were drug-resistant. From this, 43.1% are rifampicin-resistant TB (RR-TB), multidrug-resistant (MDR-TB), and extensively drug-resistant (XDR-TB). The risk factors that generated the highest probability of drug resistance were relapse (OR: 4.27; CI95% 2.94; 6.20), foreigner (OR: 3.97; CI95% 2.86; 5.52), pulmonary TB (OR: 2.92; CI95% 1.71; 4.99) and HIV (OR: 1.97; CI: 95% 1.33; 2.90). Regarding the probability of unsuccessful treatment against TB, the highest probability were street situation (OR: 3.33; CI: 95% 2.45; 4.52), drug addiction (OR: 1.91; CI 95% 1.52; 2.41), foreigner (OR: 1.51; CI 95% 1.25; 1.83), drug resistance (OR: 2.81; CI 95% 1.87; 4.20), HIV (OR: 3.24; CI: 95% 2.61; 4.02), not belonging to an indigenous people (OR: 1.43; CI 95% 1.00; 2.06) alcoholism (OR: 1.25; CI 95% 1.01; 1.54), pulmonary TB (OR: 1.43; CI 95% 1.20; 1.70) and male sex (OR: 1.44; CI 95% 1.25; 1.65). CONCLUSIONS: The risk factors identified as relapse and coinfection with HIV as predictors of drug resistance highlight the complexity of disease management. Likewise, the presence of street situations, drug addiction, and alcoholism highlights the need for specific approaches to address tuberculosis in different population groups, suggesting the need for personalized strategies.

Comparación de regímenes de linezolid, en adición a bedaquilina y pretomanida, para el manejo de tuberculosis farmacorresistente (estudio ZeNix): Lectura crítica / Comparison of linezolid regimens, in addition to bedaquiline and pretomanid, for the management of drug-resistant tuberculosis (the ZeNix study): Critical reading

RESUMEN Presentación: En el presente artículo exponemos nuestra valoración crítica de un ensayo clínico aleatorizado publicado en la revista New England Journal of Medicine el año 2022. Conclusiones del estudio: El estudio compara cuatro regímenes de linezolid (en adición a bedaquilina y pretomanid) para el manejo de tuberculosis farmacorresistente. Finalmente, se demuestra que el régimen de 600 mg de linezolid durante 26 semanas tuvo menos frecuencia de falla terapéutica y eventos adversos (en comparación con darlo por menos semanas o a más dosis). Comentario crítico: El artículo es relevante porque aún no es clara la dosis adecuada de linezolid y la duración del tratamiento con este agente para minimizar los efectos adversos y mantener la eficacia contra la tuberculosis altamente resistente. A pesar de algunas limitaciones como el bajo número de participantes, la alta pérdida al seguimiento, y el no realizar comparaciones estadísticas entre grupos; los resultados son relativamente confiables para la toma de decisiones.

ABSTRACT Presentation: In this article we present our critical appraisal of a randomized clinical trial published in the New England Journal of Medicine in 2022. Study conclusions: The study compares four linezolid regimens (in addition to bedaquiline and pretomanid) for the management of drug-resistant tuberculosis. Finally, it shows that the regimen of 600 mg of linezolid for 26 weeks had less frequency of therapeutic failure and adverse events (compared to giving it for fewer weeks or at higher doses). Critical comment: The article is relevant because the appropriate dose of linezolid and duration of treatment with this agent to minimize adverse effects and maintain efficacy against highly resistant tuberculosis is still unclear. Despite some limitations such as low number of participants, high loss to follow-up, and no statistical comparisons between groups, the results are relatively reliable for decision making.

Study of side effect profile of bedaquiline containing regimen among patients with extensively drug-resistant tuberculosis at a nodal drug-resistant center

Background: Extensively drug-resistant tuberculosis (XDR TB) is a type of tuberculosis (TB) characterized by resistance to isoniazid and rifampicin, along with resistance to one of the fluoroquinolones and at least one of the second line injectable drugs. Bedaquiline is a diarylquinoline antimycobacterial agent approved for the treatment of adults with pulmonary multidrug-resistant TB (MDR-TB) and XDR-TB by the food and drug administration. Aim and Objective: The aim of this study was to study the side effect profile of bedaquiline containing regimen among XDR TB patients. Materials and Methods: This study was conducted at outpatient and wards of nodal drug-resistant TB Center, Department of Pulmonary Medicine, SVRRGGH, Tirupati, for a period of 1 year. Forty patients of more than 18 years age and diagnosed with XDR TB were included in the study. Bedaquiline was started and daily monitoring was done with ECG and all organ function tests were repeated every 15 days. Results: All 40 cases were retreatment cases; no new XDR TB case was reported in study period. Most common age group of presentation in our study was 46 to 55 years (32.5%). Gastrointestinal adverse drug reactions were found to be more common (37.5%), cardiovascular QTc changes were observed in 10% of patients, 5% of patients had neurological reactions (Headache), 2.5% of patients had peripheral neuropathy, and 2.5% of patients had arthralgia. Conclusions: Bedaquiline containing regimen is very effective for the treatment of XDR TB cases. The study shows that compliance with this regimen is very good. Bedaquiline has minimal adverse reactions and even these are easily manageable. Bedaquiline has good safety profile and patients have improved quality of life.

Risk factors of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis / 中国基层医药

Objective:To investigate the risk factors of diabetes mellitus complicated by pulmonary tuberculosis.Methods:The clinical data of 83 patients with diabetes mellitus complicated by pulmonary tuberculosis who received treatment in Taiyuan Fourth People's Hospital from March 2020 to March 2022 were collected. These patients were divided into sensitive group ( n = 45) and resistant group ( n = 38 ) according to the results of drug sensitivity test. Univariate and multivariate non-conditional logistic regression was performed to analyze the influential factors of drug resistance. Results:Univariate logistic regression results revealed that there were significant differences in blood CD4 +T lymphocyte count ( χ2 = 11.73, P = 0.001) and diabetic complications ( χ2 = 4.94, P = 0.026). Multivariate non-conditional logistic regression analysis was performed taking whether blood CD4 +T lymphocyte count was lower than the average level and whether patients with diabetes mellitus had complications as independent variables, and taking whether drug resistance was a dependent variable. The results showed that the OR (95% CI) value of the decreased blood CD4 +T lymphocyte count was 4.909 (1.926-12.514). It is a risk factor for drug resistance of diabetes mellitus complicated by pulmonary tuberculosis. Conclusion:The decrease of blood CD4 +T lymphocyte count is a risk factor of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis, and it should be intervened early in the clinic.

Efficacy and safety evaluation of the regimen containing Bedaquiline in elderly patients with drug-resistant pulmonary tuberculosis / 中华老年医学杂志

Objective:To evaluate the efficacy and adverse reactions of the regimen containing Bedaquiline in elderly patients with multi-drug resistant tuberculosis.Methods:From March 2019 to June 2022, patients with multi-drug resistant pulmonary tuberculosis admitted to Anhui Chest Hospital were randomly divided into two groups: the observation group was given a treatment containing Bedaquiline, and the control group was given a treatment without Bedaquiline.Patients were also divided into elderly patients(age ≥60 years old)and non-elderly patients(age <60 years old)according to age.Sputum culture conversion, lesion absorption and adverse reactions were compared between the observation group and the control group in general, elderly and non-elderly patients, respectively.Results:A total of 170 cases were collected, including 79 in the observation group and 91 in the control group.Sputum culture conversion: The sputum culture conversion rates of observation groups in general, non-elderly and elderly patients were better than that of control groups at the 3rd month after treatment(the general, 96.2% vs.75.8%, χ2=14.001, P<0.001; the non-elderly, 94.9% vs.82.1%, χ2=4.675, P=0.031; the elderly, 100.0% vs. 65.7%, χ2=8.771, P=0.003), and at the 6th month, the rates of overall observation group was better than that of control group(98.7% vs.92.3%, χ2=3.895, P=0.048); the rates of non-elderly and elderly observation group and control group were all greater than 90%, with no statistical significance( P>0.05). Lesion absorption: Overall and non-elderly observation groups were better than control group in lesion absorption at the 3rd month(the general, 84.8% vs.68.1%, χ2=12.962, P=0.002; the non-elderly, 88.1% vs.71.4%, χ2=9.832, P=0.007; and the 6th month(the general, 88.6% vs.76.9%, χ2=14.888, P=0.001; the non-elderly, 89.8% vs.82.1%, χ2=8.618, P=0.013). The focal absorptivity of senile observation group at the end of March and June were 75.0% and 85.0%, respectively, both better than control group, but the difference was not statistically significant( P>0.05). Adverse reactions: Overall and non-senile observation groups had longer QT interval than control groups( P<0.05), but no patients stopped bedaquiline because of this, and there was no significant difference in QT interval between the two groups( P>0.05). Conclusions:In elderly patients with multi-drug resistant pulmonary tuberculosis, early sputum culture conversion turns fast after treatment with Bedaquiline, which has good therapeutic effect, good tolerance and controllable adverse reactions.

Drug-Resistant Tuberculosis and COVID-19: A Scoping Review on a New Threat to Antimicrobial Resistance / Tuberculosis Resistente a Medicamentos y COVID-19: Una Revisión de Alcance de una Nueva Amenaza a la Resistencia Antimicrobiana / Tuberculose droga-resistente e COVID-19: revisão de escopo de uma nova ameaça à resistência microbiana a medicamentos

ABSTRACT Objective: To assess the impact of COVID-19 on the morbidity and mortality associated with drug-resistant tuberculosis (DR-TB). Methods: A comprehensive review of articles published in international databases since December 2019 was conducted. The findings are presented in a narrative format, supplemented with tables, diagrams, and a map created using ArcGIS software. Results: Thirty-five studies were selected, highlighting the significant consequences of COVID-19 on TB and DR-TB treatment progress. Four main thematic areas were identified: Clinical and epidemiological aspects of the interaction between COVID-19 and DR-TB; Management of physical resources and the team; Challenges and circumstances; Perspectives and possibilities. Conclusions: This study revealed that the COVID-19 pandemic significantly negatively impacted the control of long-standing diseases like TB, particularly in the context of morbidity and mortality related to DR-TB.

RESUMEN Objetivo: Evaluar el impacto de COVID-19 en la morbilidad y mortalidad asociada con la tuberculosis resistente a medicamentos (DR-TB). Métodos: Se realizó una revisión integral de artículos publicados en bases de datos internacionales desde diciembre de 2019. Los hallazgos se presentaron de forma narrativa, complementados con tablas, diagramas y un mapa creado con el software ArcGIS. Resultados: Se seleccionaron 35 estudios que destacaron las consecuencias significativas de COVID-19 en el progreso del tratamiento de la TB y la DR-TB. Se identificaron cuatro áreas temáticas principales: "Aspectos clínicos y epidemiológicos de la interacción entre COVID-19 y DR-TB", "Gestión de recursos físicos y del equipo", "Desafíos y circunstancias" y "Perspectivas y posibilidades". Conclusiones: Este estudio reveló que la pandemia de COVID-19 tuvo un impacto negativo significativo en el progreso del control de enfermedades antiguas como la TB, especialmente en el contexto de la morbilidad y mortalidad relacionada con la DR-TB.

RESUMO Objetivo: Avaliar o impacto da COVID-19 na morbimortalidade associada à tuberculose resistente a medicamentos (DR-TB). Métodos: Realizou-se uma revisão abrangente de artigos publicados em bases de dados internacionais a partir de dezembro de 2019. As evidências foram apresentadas de maneira narrativa, com o suporte de tabelas, diagramas e um mapa elaborado no software ArcGIS. Resultados: Foram selecionados 35 estudos que destacaram as consequências significativas da COVID-19 nos avanços no tratamento da TB e da DR-TB. Quatro áreas temáticas foram identificadas: "Aspectos clínicos e epidemiológicos da interação entre COVID-19 e DR-TB", "Gestão de recursos físicos e da equipe", "Desafios e circunstâncias" e "Perspectivas e potencialidades". Conclusões: Este estudo evidenciou que a pandemia de COVID-19 teve um impacto negativo significativo na progressão do controle de uma doença ancestral como a TB, especialmente no contexto da morbimortalidade por DR-TB.

The first successful cochlear implant in Latin America after severe aminoglycoside-induced ototoxicity in a Peruvian patient cured of extensively drug-resistant tuberculosis

Introduction: Multidrug-resistant tuberculosis is a significant public health problem for which drugs are used with many adverse effects. Among the devastating consequences of these diseases, there is a wide variation in the incidence of ototoxicity and hearing loss in patients with multidrug-resistant and extremely resistant tuberculosis. Cochlear implants may be indicated in patients with unilateral/severe bilateral hearing loss with no benefit from conventional hearing aids, but their use in patients with tuberculosis is rare. Case report: We present the first case of a right unilateral cochlear implant performed on a 34-year-old Peruvian patient who presented profound sensorineural hearing loss of cochlear origin. Conclusion: Cochlear implant surgery is an essential milestone in the treatment of patients with auditory sequelae of tuberculosis treatment. Close monitoring of possible complications of tuberculosis treatment should be strengthened in countries with a high incidence of multidrug-resistant and extremely resistant tuberculosis.

Introducción: La tuberculosis multidrogorresistente es un importante problema de salud pública para el que se utilizan fármacos con múltiples efectos adversos. Entre las devastadoras consecuencias de estas enfermedades, existe una amplia variación en la incidencia de ototoxicidad y pérdida auditiva en pacientes con tuberculosis multirresistente y extremadamente resistente. Los implantes cocleares pueden estar indicados en pacientes con pérdida auditiva unilateral/bilateral severa sin beneficio de los audífonos convencionales, pero su uso en pacientes con tuberculosis es raro. Reporte de un caso: Presentamos el primer caso de implante coclear unilateral derecho realizado a un paciente peruano de 34 años que presentaba hipoacusia neurosensorial profunda de origen coclear. Conclusión: La cirugía de implante coclear es un hito fundamental en el tratamiento de los pacientes con secuelas auditivas del tratamiento de la tuberculosis. Se debe fortalecer la vigilancia estrecha de las posibles complicaciones del tratamiento de la tuberculosis en los países con una alta incidencia de tuberculosis multirresistente y extremadamente resistente.

Resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en el departamento del Atlántico, 2013-2016 / Resistance of Mycobacterium tuberculosis to quinolone and injectable drugs in Atlántico department, 2013-2016

Introducción: En el departamento del Atlántico los estudios de resistencia del Mycobacterium tuberculosis se han limitado a drogas de segunda línea. Objetivo: Determinar prevalencia de resistencia a amikacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas drogas, en el periodo 2013 a 2016 en el departamento del Atlántico. Métodos: Estudio transversal de 194 aislamientos resistentes a isoniacida, rifampicina o ambas, por metodología Genotype MTBDR plus versión 2, enviados al Instituto Nacional de Salud en el periodo 2013 al 2016 para ser confirmados y procesados para drogas de segunda línea. La proporción de resistencia, se hizo según variables sociodemográficas, clínica y de vigilancia en salud pública. Resultados: Las comorbilidades frecuentes encontradas fueron desnutrición con el 18,56 por ciento, seguido de infección concomitante VIH-tuberculosis con el 13,40 por ciento. La ofloxacina en casos no tratados obtuvo la mayor resistencia global con el 1,50 por ciento (IC 95 por ciento 0,18-5,33). En los que fueron previamente tratados la resistencia global a capreomicina fue del 8,10 por ciento (IC 95 por ciento 2,7-17,8). En los resistentes a rifampicina, un caso fue extensivamente resistente y dos casos resistentes en los multidrogorresistente. Conclusiones: Se encontró baja resistencia a fluoroquinolonas y fármacos inyectables en pacientes no tratados resistentes a isoniacida, rifampicina o ambas, que muestra que todavía no constituye un problema mayor en el departamento del Atlántico. Se debe complementar su seguimiento con buen manejo tanto físico como psicológico y un equipo de salud fortalecido que actúe prontamente y ayude a la adherencia del paciente a los tratamientos(AU)

Introduction: In Atlántico department, resistance studies of Mycobacterium tuberculosis have been limited to second-line drugs. Objective: Determine prevalence of resistance to amikacin, kanamycin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid, rifampicin or both, in the period 2013 to 2016 in Atlántico department. Methods: Cross-sectional study of 194 isolations resistant to isoniazid, rifampicin or both, by Genotype MTBDR plus version 2 methodology, that were sent to the National Institute of Health from 2013 to 2016 to be confirmed and processed for second-line drugs. The resistance ratio was made according to sociodemographic, clinical and public health surveillance variables. Results: The common comorbilities found were malnutrition with 18.56 percent, followed by concomitant HIV-tuberculosis infection with 13.40 percent. Ofloxacin in non-treated cases achieved the highest overall resistance with 1.50 percent (95 percent CI 0.18-5.33). In those previously treated, global resistance to capreomycin was 8.10 percent (95 percent CI 2.7-17.8). In the ones resistant to rifampicin, one case was extensively resistant and two cases were resistant in multi-drugs resistant. Conclusions: Low resistance to fluoroquinolones and injectable drugs was found in non-treated patients who were resistant to isoniazid, rifampicin or both, showing that it is not yet a major problem in Atlántico department. Its follow-up should be complemented with good physical and psychological management and a strengthened health team that acts promptly and helps the patient adherence to treatments(AU)

Clinical outcomes and molecular characterization of drug-resistant tuberculosis in pre- and extensively drug-resistant disease based on line probe assays

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) represents a significant impact in transmission, outcome, and health costs. The World Health Organization recommends implementation of rapid diagnostic methods for multidrug-resistance detection. This study was performed to evaluate the frequency of pre- and extensively drug resistant tuberculosis (pre-XDR-TB and XDR-TB) among MDR-TB patients, the pattern of resistance mutations for fluoroquinolones and the clinical outcome. Adult patients followed at a Brazilian regional reference center for TB, from January 2013 to June 2019 were included. Stored Mycobacterium tuberculosis (Mtb) cultures were recovered, the DNA was extracted, and the susceptibility test was performed using the line probe assay for second line antimycobacterial drugs, Genotype MTBDRsl version 2.0 (Hain Lifescience, CmbH, Germany). Among 33 MDR-TB included patients, we diagnosed XDR-TB or pre-XDR in five (15%) cases. Of these, mutations related to fluoroquinolones resistance were observed in four Mtb isolates, including one who had no phenotypic resistance profile. In two other patients with phenotypic resistance to ofloxacin, genotypic resistance was not found. Case fatality rate was 60% in pre/XDR-TB group, compared to 3.6% in the remaining of patients. This study observed few cases of pre-XDR and XDR-TB among a MDR-TB cohort. Phenotypic and genotypic assays presented good agreement. Clinical outcome was more favorable for patients with susceptibility to fluoroquinolones and injectable drugs.

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis / Los resultados adversos en el tratamiento de la tuberculosis resistente a múltiples fármacos sobrepasan la relación fármaco-microorganismo: resultados de un análisis de correspondencia múltiple

Abstract . Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities. Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia. Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease. Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Resumen . Introducción. El tratamiento de la tuberculosis multirresistente tiene una efectividad del 50 %, afectado por múltiples factores como la sensibilidad del microorganismo, las reacciones secundarias, los factores sociales y las comorbilidades existentes. Objetivos. Describir la demografía, las características clínicas y los factores pronósticos asociados con los resultados del tratamiento en pacientes multirresistentes (TB-MDR) de Medellín, Colombia. Métodos. Se hizo un análisis retrospectivo de los datos de los pacientes con TB-MDR atendidos en el Hospital La María de Medellín, Colombia, que fueron tratados entre el 2010 y el 2015. Los pacientes se categorizaron con tratamiento exitoso (curados) o con tratamiento fallido (falla en el tratamiento, pérdida durante el seguimiento y muerte). Se determinó la asociación entre las características demográficas y clínicas, los resultados de los exámenes de laboratorio, los desenlaces del tratamiento y la información del seguimiento, utilizando análisis univariado, multivariado y de correspondencia múltiple. Resultados. De 128 pacientes con TB-MDR, 77 (60 %) tuvieron un tratamiento exitoso. De los que tuvieron un tratamiento fallido, 26 pacientes se perdieron en el seguimiento, 15 murieron y 10 tuvieron falla en el tratamiento. El tratamiento irregular, las comorbilidades y los cultivos positivos más allá de 2 meses de tratamiento se asociaron significativamente con los tratamientos fallidos (p<0,05). El análisis de correspondencia múltiple agrupó los pacientes con pérdida en el seguimiento, con HIV y tratamientos irregulares, y los pacientes con tratamientos irregulares y enfermedad pulmonar obstructiva crónica con falla en el tratamiento y muerte. Conclusión. El reconocimiento temprano de los factores que afectan el desenlace del tratamiento de los pacientes con TB-MDR es esencial; la identificación de dichos factores debería incrementar el éxito del tratamiento y contribuir al adecuado control de la TB-MDR.

Serie de casos: tuberculosis extremadamente resistente a drogas en Colombia, 2006-2016 / Extensively resistant tuberculosis, Colombia, 2006-2016

Introducción. La tuberculosis extremadamente resistente a los medicamentos (TB-XDR) es el resultado de deficiencias en la administración del tratamiento y en la prevención de la transmisión de la enfermedad; además, es un reto para los programas nacionales de control de la tuberculosis. Objetivo. Describir las características clínicas y epidemiológicas de los casos de TB-XDR diagnosticados en Colombia. Materiales y métodos. Se trata de un estudio de serie de casos, de pacientes con diagnóstico de TB-XDR, de 2006 a 2016 en Colombia. Las fuentes de información fueron el formato único de vigilancia y la base de datos del Laboratorio Nacional de Referencia. Se analizaron las variables: entidad territorial de procedencia, sexo, edad, régimen de afiliación, forma de tuberculosis, coinfección tuberculosis-HIV, patrón de sensibilidad a los fármacos de segunda línea y resultado (vivo o muerto). Resultados. En el período de estudio, se diagnosticaron 51 casos de TB-XDR, 28 hombres y 23 mujeres, con un promedio anual de cinco casos. En los departamentos de Antioquia, Valle del Cauca y Atlántico, se presentaron 46 (90 %) de los casos. El rango de edad fue de 5 a 81 años y, la mediana, de 40 años. De los 51 pacientes, 32 (63 %) estaban afiliados al régimen subsidiado de salud y 46 (90 %) presentaron tuberculosis pulmonar; de los 22 a quienes se les practicó la prueba para HIV, en tres (13,6 %) había coinfección con HIV, y 29 (57 %) murieron. Los fármacos a los cuales hubo mayor resistencia, fueron ofloxacina en 45 (88 %) casos y amikacina en 43 (84 %). Conclusión. La TB-XDR se presentó principalmente en formas pulmonares, lo cual aumenta la probabilidad de transmisión en la comunidad y se refleja en la aparición de tuberculosis resistente en menores de 15 años. La población más afectada es la económicamente activa, con una gran mortalidad. El Programa Nacional de Prevención y Control de la Tuberculosis debe generar estrategias para evitar la propagación de cepas resistentes.

Introduction: Extensively drug-resistant tuberculosis (XDR-TB) is a result of deficiencies in the administration of treatment and transmission of the disease, being a challenge for national programs of tuberculosis control. Objective: To describe the clinical and epidemiological characteristics of the cases diagnosed in Colombia. Materials and methods: Case series study, performed on people diagnosed with XDRTB during 2006 to 2016 in Colombia. Information source: unique surveillance format and database of the national reference laboratory. The variables territorial entity of origin, gender, age, affiliation regime, form of tuberculosis, tuberculosis-HIV coinfection, sensitivity pattern to second line drugs and live/dead outcome were analyzed. Results: In this period, 51 XDR-TB cases have been diagnosed, with an annual average of five cases. Antioquia, Valle del Cauca and Atlántico present 90% (46) of cases. Age range: 5 to 81 years, median: 40 years. There were 28 men (55%) of the cases. Subsidized affiliation regime: 63% (32/51). Pulmonary form: 90% (46/51). TB-HIV coinfection: 13.6% (3/22). The drugs with greater resistance: ofloxacin 90% (45/51) and amikacin 86% (43/51). Dead unlink: 57% (29/51). Conclusion: XDR-TB occurred mainly in pulmonary forms increasing the probability of transmission in the community, which is reflected in the appearance of resistance in children under 15 years of age. The most affected population is economically active, with high mortality. The national program of tuberculosis control must generate strategies to avoid the spread of resistance that is affecting children and the economically active population, with high mortality.

Vigilancia por el laboratorio de la tuberculosis resistente en menores de 15 años, Colombia, 2010 a 2015 / Resistant tuberculosis in children under 15 years of age, Colombia 2010-2015

Resumen Introducción. La tuberculosis en los niños es un reflejo de transmisión reciente en la comunidad. Se estima que en el mundo cada año un millón de niños enferma por esta causa; en Colombia se notificaron 291 casos en el 2015. Objetivo. Actualizar la información obtenida de las actividades de vigilancia por el laboratorio de la farmacorresistencia del bacilo Mycobacterium tuberculosis en menores de 15 años en Colombia entre el 2010 y el 2015. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de corte transversal. Se estudiaron las variables de procedencia, sexo, edad, tipo de tuberculosis y estado de HIV en los casos sensibles y resistentes. Estos se clasificaron como caso nuevo sin tratamiento o caso previamente tratado para analizar el perfil de resistencia a fármacos de primera y segunda línea. Resultados. De los 3.440 casos notificados, en el 16,4 % se practicó la prueba de sensibilidad. El 50,6 % eran mujeres, la forma pulmonar se presentó en el 70,6 % y el 1,4 % presentó coinfección de tuberculosis y HIV. Se estudiaron 565 casos, de los cuales 503 (89,0 %) eran nuevos: el 3,9 % con tuberculosis multirresistente y el 9,5 % con resistencia global. Los previamente tratados fueron 62 (10,9 %), 4,8 % con multirresistencia y 19,3 % con resistencia global. No se evidenciaron diferencias estadísticamente significativas en los años estudiados. La proporción de tuberculosis extremadamente resistente en los casos nuevos evaluados fue de 9,0 %. Conclusiones. Es necesario que el Ministerio de Salud y Protección Social y el Instituto Nacional de Salud promuevan el uso de pruebas diagnósticas rápidas y muy sensibles, como las moleculares recomendadas por la Organización Mundial de la Salud.

Abstract Introduction: Tuberculosis in children is a recent transmission reflection in the community. It is estimated that every year one million children get sick in the world because of this. In Colombia, 291 cases were notified in 2015. Objective: To update the information obtained from the surveillance activities of the drug-resistance laboratory in children younger than 15 years of age in Colombia between 2010 and 2015. Materials and methods: This was a cross-sectional retrospective study. We studied the variables of origin, gender, age, type of tuberculosis, and HIV status in sensitive and resistant cases. We classified them according to their treatment background between new and previously treated to analyze their first and second line drug resistance profile. Results: From the notified cases, 16.4 % had a sensitivity test. 50.6 % were women, the pulmonary form was present in 70.6% cases, and 1.4 % presented with tuberculosis/HIV coinfection. We studied 565 cases, from which 503 (89.1 %) were new, presenting with multidrug-resistant tuberculosis, and a global resistance of 3.9 % and 9.5 %, respectively. From them, 62 had been previously treated (10.9 %), with 4.8 % and 19.3 % multidrug resistance and global resistance, respectively. There was no evidence of statistically significant differences during the studied years. Extremely resistant tuberculosis in new cases was 9.0 %. Conclusions: It is necessary for the Ministerio de Salud y Protección Social and the Instituto Nacional de Salud to promote the use of faster and more sensitive diagnostic tests such as the molecular ones recommended by the World Health Organization.

High degree of fluoroquinolone resistance among pulmonary tuberculosis patients in New Delhi, India

Background & objectives: The fluoroquinolones (FQs) group of antibiotics is the backbone drugs for the management of drug-resistant tuberculosis (TB). In routine clinical practice, drug susceptibility testing (DST) for FQs is not performed, and the patients are empirically treated. A limited information exists regarding FQs resistance among pulmonary TB cases. The present study was conducted to determine the FQs resistance among drug sensitive and drug-resistant pulmonary TB patients in a tertiary care centre in north India. Methods: A total of 1619 sputum/smear-positive specimens of pulmonary TB patients were subjected to DST for first-line drugs (FLDs) and second-line drugs. In addition, FQs DST was also performed using automated Mycobacterial Growth Indicator Tube-960 liquid culture technique. The immuno-chromatographic assay was performed to distinguish Mycobacterium tuberculosis complex (MTBC) from non-MTBC. Results: Mycobacterium tuberculosis (Mtb) was isolated in 1499 sputum specimens; 1099 culture specimens were sensitive to FLDs, 249 grew as multidrug-resistant (MDR) Mtb and the remaining 151 isolates revealed any drug resistance to FLDs. While FQs monoresistance among the FLD sensitive isolates was 3.1 per cent (35/1099), 27.3 per cent (68/249) among MDR Mtb isolates had additional FQs resistance. Interpretation & conclusions: FQs resistance among drug sensitive and MDR Mtb isolates was high in Delhi, India. Based on these findings, it is recommended that the DST for FQs should be routinely performed to avoid further amplification of drug resistance.

Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation / Tratamento da tuberculose grave e suas sequelas: da terapia intensiva à cirurgia e reabilitação

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

RESUMO A tuberculose multirresistente e a tuberculose extensivamente resistente ainda são um desafio para médicos e especialistas em saúde pública. Os desfechos globais do tratamento ainda são insatisfatórios; apenas 54% dos pacientes têm um desfecho positivo. Os desfechos globais são ainda piores em pacientes infectados por cepas altamente resistentes. O tratamento da tuberculose multirresistente/extensivamente resistente é difícil em virtude dos eventos adversos frequentes, da longa duração dos esquemas terapêuticos, do alto custo dos medicamentos de segunda linha, das sequelas pós-infecciosas crônicas e da perda da função orgânica. Esforços de pesquisa (estudos e ensaios) estão em andamento e têm diversos objetivos: aumentar as taxas de sucesso do tratamento; compreender o potencial de medicamentos novos e reaproveitados; encurtar o tratamento e reduzir as taxas de eventos adversos. Espera-se que melhor acesso ao diagnóstico rápido, maior conhecimento e terapias mais eficazes reduzam as complicações e o comprometimento da função pulmonar. O objetivo deste artigo é discutir o tratamento da tuberculose grave (potencialmente fatal, que necessita de níveis maiores de atenção) e suas sequelas, desde a terapia intensiva até o pós-operatório, reabilitação e recuperação. São também discutidas as intervenções não farmacológicas disponíveis para tratar sequelas crônicas e melhorar a qualidade de vida dos pacientes. Como a maioria dos casos de tuberculose multirresistente/extensivamente resistente resulta em comprometimento da função pulmonar (obstrução principalmente, mas às vezes restrição), qualidade de vida prejudicada e desempenho reduzido (medido por meio de testes de caminhada ou outros), são necessárias outras intervenções (cessação do tabagismo, reabilitação pulmonar, vacinação e prevenção de infecções bacterianas secundárias/exacerbações, por exemplo, complementadas por apoio psicológico e nutricional).

Tuberculosis congénita pre-extensivamente resistente a drogas: reporte de caso / Pre-extensively drug-resistant congenital tuberculosis: case report

RESUMEN La tuberculosis en el lactante es un cuadro de difícil diagnóstico por las pruebas diagnósticas que muchas veces resultan negativas y por la dificultad de identificar la fuente de transmisión. Se presenta el caso de un lactante varón de un mes de vida que presenta irritabilidad, taquipnea, fiebre, pobre ganancia de peso desde el nacimiento y hepatomegalia, además, tiene el antecedente materno de tuberculosis pre-extensivamente resistente a drogas y reacción granulomatosa tuberculoide con tinción auramina positiva para bacilos ácido-alcohol resistentes en la histopatología de placenta. Ante la sospecha de tuberculosis congénita, es referido al Instituto Nacional de Salud del Niño para estudio diagnóstico y tratamiento; el paciente presenta una evolución clínica favorable y sin reacciones adversas al tratamiento. El diagnóstico de tuberculosis congénita debe considerarse en lactantes con signos clínicos sugestivos de la enfermedad y mantener la sospecha ante la presencia del antecedente materno de infección por Mycobacterium tuberculosis.

ABSTRACT Tuberculosis in infants is a clinical case difficult to diagnose by regular testing which often yield negative results; additionally, the source of transmission is difficult to identify. This work presents the case of a one-month old nursing boy presenting irritability, tachypnea, fever, poor gain weight from birth, and hepatomegaly. Additionally, he had the maternal history of pre-extensively drug- resistant tuberculosis and tuberculoid granulomatosis reaction with positive auramine tincture for acid-alcohol resistant bacilli at histopathology of the placenta. With a suspected congenital tuberculosis, he was referred to the National Children's Health Institute for diagnosis and treatment. The patient showed a favorable clinical evolution and no adverse reactions to treatment. The diagnosis of congenital tuberculosis must be considered in infants with suggestive clinical signs of the disease and such suspicion must be maintained with the presence of a maternal history of Mycobacterium tuberculosis infection.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis / Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente

ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

RESUMO A tuberculose multirresistente (TB-MDR, do inglês multidrug-resistant) e a extensivamente resistente (TB-XDR, do inglês extensively drug-resistant) continuam representando um desafio para os clínicos e as autoridades de saúde pública. Infelizmente, embora haja relatos encorajadores de taxas de sucesso maiores, a taxa global de desfechos favoráveis do tratamento da TB-MDR/XDR é de apenas 54%, ou muito menor quando o espectro de resistência aos fármacos vai além do da TB-XDR. O tratamento da TB-MDR/XDR continua sendo uma tarefa difícil, em razão da alta incidência de eventos adversos, do longo tempo de tratamento, do alto culto dos esquemas utilizados e da drenagem dos recursos de saúde. Diversos ensaios e estudos foram realizados recentemente (alguns já publicados e outros em andamento), todos visando a melhorar os desfechos do tratamento da TB-MDR/XDR por meio da alteração da abordagem geral, redução do tempo de tratamento e desenvolvimento de um esquema universal. O objetivo desta revisão foi resumir o que se conseguiu até o momento, no que se refere a novos fármacos e fármacos repropostos, dando foco especial para delamanid, bedaquilina, pretomanida, clofazimina, carbapenêmicos e linezolida. Após mais de 40 anos de negligência, recentemente foi dada mais atenção á necessidade de novos fármacos para se combater a "praga branca", e resultados promissores estão sendo relatados.

Rapid detection of drug resistance in mycobacterium tuberculosis using Tag Array chip / 中华骨科杂志

Objective To evaluate the sensitivity and specificity of Tag Array in detecting the clinical isolates of bone and joint tuberculosis.Methods Twenty-four strains of Mycobacterium tuberculosis having sequence differences in extracted plasmids of mutant strains.The plasmid was diluted into different concentrations,and then multiplex PCR amplification was performed to analyze the sensitivity and specificity of the chip system.A total of 187 clinical isolates were collected from patients with bone and joint tuberculosis.Among them,there were 50 strains of sensitive bacteria,and 137 strains of drug-resistant.Designed,optimized and prepared chip inspection system,sequencing and phenotypic drug susceptibility results were analyzed to evaluate the sensitivity and specificity of the gene chip.Results The mutants in accordance with sequencing result in the sets with 1 × 103copy/μl of template concentration and above;while 29 sets showed false negative result in the sets with 1 × 102 copy/μl.Among the 126 rifampicin phenotype drug resistance strains,119 strains appeared mutation in rpoB gene.In the rifampicin phenotype sensitivity strains,9 strains of rpoB gene showed mutation,the sensitivity was 94.40％,and specificity was 86.76％.Among the 118 isoniazid phenotype drug resistance strains,109 strains appeared mutation in relevant drug resistance gene locus,the sensitivity was 92.37％,and specificity was 81.16％.Among the 44 ethambutol phenotype drug resistance strains,27 strains appeared mutation in locus embB306,in the ethambutol phenotype sensitivity strains,the mutation in locus embB306 was detected in 6 strains,the sensitivity was 61.36％,and specificity was 95.80％.Among the 102 levofloxacin phenotype drug resistance strains,81 strains appeared mutation in gyrA gene,4 of the sensitivity strains were detected mutation in gyrA gene,the sensitivity was 79.41％,and specificity was 95.29％.Among the 112 streptomycin phenotype drug resistance strains,the chip detected 101 strains appeared mutation,the sensitivity of chip detection was 90.17％,and specificity was 84.00％.Since amikacin,capreomycin and kanamycin are in cross drug resistance,among the 67 phenotype drug resistance strains,52 strains appeared mutation in relevant drug resistance gene locus,its sensitivity was 79.10％ and specificity was 90.83％.Conclusion Tag Array chip can achieve rapid,accurate and high-throughput detection of tuberculosis resistance,which has important clinical significance and feasibility.

Clinical efficacy of compound sulfamethoxazole combined with second-line drugs in treatment of MDR-TB / 重庆医学

Objective To investigate the effect of compound sulfamethoxazole(SMZ.Co) combined with second-line drugs in the treatment of multiple drug-resistant tuberculosis(MDR-TB).Methods Eighty-five cases of MDR-TB collected in this hospital from March 2014 to December 2016 were divided into the group A,B and C group.The C group underwent the conventional secondline anti-TB treatment,on this basis the group A and B were additionally added with 0.96 g and 0.48 g SMZ.Co respectively.The clinical curative effects(such as cough,phlegm,sputum bacterial negative conversion rate and X-rays) were compared among the three groups.Results Compared with C group,the cough and phlegm rates after continuous treatment for six months in the group A and B treated by combined use of SMZ.Co were significantly decreased,the difference was statistically significant(P＜0.05),while the sputum bacterial negative conversion rate,change of lesion focus and cavity,and treatment outcome rate had no statistical difference(P＞0.05).Conclusion The application of SMZ.Co combined with second-line drugs in the treatment of MDR-TB could effectively relieve the symptom of cough and phlegm.