Clinical and epidemiological features of tuberculosis isolated from critically ill patients / Tuberculosis en la unidad de cuidados intensivos: características clínicas y epidemiológicas

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p;<;0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p;<;0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.

La tuberculosis (TB) aún representa un problema mayor de salud pública. En Uruguay, contrariamente a la tendencia mundial, se ha observado un incremento en el número de casos desde 2006. Aunque la incidencia de casos de multidrogorresistencia (MDR) es baja y no se han reportados casos de resistencia a fármacos de primera y segunda línea de tratamiento (XDR), se ha observado un incremento en el número de casos con TB grave, que requieren internación en unidad de terapia intensiva (CTI). Como primer objetivo del presente trabajo, se analizó la estructura genética de cepas de Mycobacterium tuberculosis aisladas de pacientes internados en CTI. Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad. Observamos un incremento estadísticamente significativo del genotipo Haarlem en los pacientes internados en CTI (53,3 vs. 34,7%; p;<;0,05). Además, investigamos la asociación del desenlace clínico con el genotipo, y encontramos una mayor incidencia de disfunción hepática en los pacientes infectados con la cepa Haarlem (p;<;0,05). La cohorte presentada en este trabajo corresponde a una de las series con mayor número de pacientes con tuberculosis que requirieron internación en CTI.

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.

Seguridad y eficacia de linezolid en el tratamiento de tuberculosis extremadamente resistente / Safety and efficacy of linezolid in the treatment of extremely resistant tuberculosis

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del medicamento linezolid, respecto a su uso en pacientes con tuberculosis extremadamente resistente (TB- XDR). Aspectos Generales: La tuberculosis continúa siendo un problema de salud pública mundial importante. A pesar que la incidencia de TB está disminuyendo globalmente aproximadamente 2% cada año y la mortalidad relacionada con la TB disminuyo un 45% entre los años 1995 y 2012, el número de casos de TB en el mundo es aún ingente, con 8.6 millones de personas con la enfermedad y 1.3 muertes en el 2012. Además, los casos de tuberculosis multidrogo resistente (TB-MDR) y tuberculosis extremadamente resistente (TB-XDR) presentan nuevos y enormes retos para el manejo y control de esta enfermedad. Tecnologia Sanitaria de Interés: Linezolid: El Linezolid pertenece a la clase de antibióticos denominada oxazolidinonas. Este medicamento se une a la subunidad ribosomal 50S inhibiendo la formación del complejo de iniciación y previniendo la traducción y síntesis de proteínas. Este mecanismo de acción tiene la ventaja de limitar la reacción cruzada con otros inhibidores de la síntesis de proteínas, haciéndolo atractivo para las infecciones resistentes. METODOLOGÍA: Estrategia de Búsqueda: La búsqueda de la literatura respecto a la eficacia y seguridad de linezolid para el \r\ntratamiento de pacientes con TB-XDR incluyo la búsqueda de guías de práctica clínica, evaluaciones de tecnologías sanitarias, revisiones sistemáticas y estudios primarios. La búsqueda de GPC se realizó en las páginas de internet de la Organización Mundial de la Salud, de los Centros para el Control y Prevención de las Enfermedades (CDC), la National Institute for Health and Care Excellence (NICE), la Scottish Intercollegiate Guidelines Network (SIGN) y el repositorio creado por la agencia para la investigación \r\nen salud y calidad (Agency for Healthcare Research and Quality (AHRQ)). Se utilizaron las bases creadas por NICE, SIGN y Cochrane para la búsqueda de evaluaciones de tecnología sanitaria. La búsqueda de las revisiones sistemáticas y los estudios primarios fueron realizados en las bases de datos de OVID MEDLINE y TRIPDATABASE. RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso del linezolid en los esquemas de tratamiento antituberculoso para pacientes adultos y niños \r\ncon TB-XDR. Guías Clínicas: la búsqueda identificó tres guías desarrolladas por la OMS para el manejo de la tuberculosis multidrogo resistente: la guía de la OMS para el manejo programático de la tuberculosis resistente 2008, la guía de la OMS para el manejo programático de la tuberculosis resistente 2011, y la guía de la OMS para los programas nacionales de tuberculosis para el manejo de la tuberculosis en los niños 2014. Evaluaciones de tecnología sanitaria: no se identificó alguna evaluación del medicamento de linezolid como tratamiento antituberculoso. Revisiones sistemáticas: se identificaron tres revisiones sistemáticas que examinaron los efectos de beneficio y de daño del uso de linezolid en pacientes con TB-DR. Ensayos clínicos: se incluyó un ensayo controlado aleatorizado que evaluó la eficacia y seguridad del uso de linezolid en pacientes adultos con TB-XDR. Otros estudios: se incluyeron una revisión narrativa que describió los resultados de reportes de casos del uso de linezolid en pacientes pediátricos con TB-DR. Ensayos Clínicos registrados en www.clinicaltrials.gov: no se identificaron estudios registrados que tengan como objetivo evaluar los efectos del linezolid en pacientes con TB-XDR. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se identificó evidencia de baja calidad respecto a los efectos de beneficio y de daño de los regímenes que contienen linezolid comparado con los regímenes sin linezolid. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, aprueba temporalmente el uso del linezolid para el tratamiento de pacientes con TB-XDR. Dado que la evidencia que respalda este uso de linezolid dentro de los esquemas \r\nantituberculosos para casos de TB-XDR es aún limitada, se establece que el efecto de la aprobación del linezolid para su uso en el tratamiento de TB-XDR se evaluará con los datos de los pacientes que hayan recibido el esquema por el lapso de dos años para determinar el impacto de su uso en varios desenlaces \r\nclínicos. Esta información será tomada en cuenta en la re-evaluación de este medicamento para efectos de un nuevo dictamen al terminar la vigencia del presente Dictamen Preliminar.

Emerging strategies for the treatment of pulmonary tuberculosis: promise and limitations?

A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed.

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases / O desafio do tratamento da tuberculose extensivamente resistente em um hospital de referência no estado de São Paulo: um relato de três casos

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

RESUMO Relatamos aqui os casos de três pacientes portadores de tuberculose extensivamente resistente, internados em um hospital de referência no estado de São Paulo, e mostramos sua evolução clínica, radiológica e laboratorial pelo período de um ano. O tratamento instituído foi baseado nas diretrizes da Organização Mundial da Saúde, com a inclusão de uma nova proposta de uso de uma associação de drogas antituberculose (linezolida e imipenem). Nos casos estudados, demonstrou-se o desafio de construir um esquema terapêutico aceitável e eficiente com drogas mais tóxicas, mais dispendiosas e que foram utilizadas por períodos mais prolongados. Mostramos também o importante acréscimo nos custos do tratamento desses pacientes, com possíveis impactos no sistema de saúde mesmo após a alta hospitalar. Ressaltamos que, em casos extremos como os apresentados neste estudo, a hospitalização em centros de referência mostrou-se o caminho mais efetivo para oferecer tratamento adequado com possibilidade de cura. Em conclusão, todos os esforços dos profissionais da saúde e do poder público devem ser direcionados a evitar casos de tuberculose multirresistente e extensivamente resistente.

Drug-resistance pattern of Mycobacterium tuberculosis strains from patients with pulmonary and extrapulmonary tuberculosis during 2006 to 2013 in a Korean tertiary medical center

BACKGROUND/AIMS: We evaluated the trend in the rates of drug-resistant tuberculosis (TB) over time, as well as the difference in the drug-resistance pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) at a private referral center in South Korea. METHODS: All patients with culture-confirmed TB from 2006 to 2013 were included. RESULTS: In total, 1,745 patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of previously treated cases, respectively. The MDR TB rate during the study period decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in previously treated cases. No difference in the drug-resistance rate was detected between PTB and EPTB. CONCLUSIONS: The TB drug-resistance rate, particularly that of MDR TB, remained high at a private referral hospital, and the drug-resistance rate did not decrease significantly from 2006 to 2013. This finding underscores the need for a national survey regarding the prevalence of drug-resistant TB to obtain the most accurate and current drug-resistance status in South Korea, including the private sector.

XDR-TB: An outcome of programmatic management of TB in India.

A significantly strengthened Revised National Tuberculosis Control Programme (RNTCP) is currently operational in India. In this case-based commentary, we describe the plight of a patient who developed extensive drug-resistant tuberculosis (XDR-TB) despite having received treatment under the RNTCP for a long period. Our aim is to analyse the programmatic management of tuberculosis in India by highlighting and discussing various issues related to the treatment received by the patient. Further, the article explores whether there is a need to incorporate an ethical element into the RNTCP as it stands today.

New approaches in the diagnosis and treatment of susceptible, multidrug-resistant and extensively drug resistant tuberculosis

Tuberculosis [TB] is killing nearly two million people worldwide every year. The current global burden of TB is mainly due to the expanding human immunodeficiency virus infection and its association with active TB disease and increasing resistance of Mycobacterium tuberculosis strains to most-effective [first-line] anti-TB drugs. Incomplete/ improper treatment of TB patients leads to evolution of drug-resistant M. tuberculosis strains as a result of chromosomal mutations in genes encoding drug targets. Sequential accumulation of mutations in target genes generate multidrug-resistant [resistant atleast to rifampin and isoniazid] M. tuberculosis [MDR-TB] and extensively drug-resistant [additionally resistant to fluoroquinolones and an injectable anti-TB agent] M. tuberculosis [XDR-TB] strains. While proper treatment of susceptible TB has > 95% cure rate, effective treatment of MDR-TB is difficult in developing countries as it is heavily dependent on rapid diagnosis, supervised aggressive therapy with several [5 - 6] expensive, toxic and less efficacious drugs for 18 - 24 months and regular monitoring for bacteriological and clinical improvement. Treatment of XDR-TB is far more difficult even in developed countries. Several anti-TB drugs with novel mechanism of action are under clinical development, which may shorten treatment duration of susceptible TB to around three months and also help in effective treatment of MDR-TB / XDR-TB

Retrospective Comparison of Levofloxacin and Moxifloxacin on Multidrug-Resistant Tuberculosis Treatment Outcomes

BACKGROUND/AIMS: To compare the effect of levofloxacin and moxifloxacin on treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: A retrospective analysis of 171 patients with MDR-TB receiving either levofloxacin or moxifloxacin was performed. Treatment responses were categorized into treatment success (cured and treatment completed) or adverse treatment outcome (death, failure, and relapsed). RESULTS: The median age of the patients was 42.0 years. Approximately 56% of the patients were male. Seventeen patients had extensively drug-resistant tuberculosis, and 20 had a surgical resection. A total of 123 patients (71.9%) received levofloxacin for a median 594 days, and 48 patients (28.1%) received moxifloxacin for a median 673 days. Other baseline demographic, clinical, and radiographic characteristics were similar between the two groups. The moxifloxacin group had a significantly higher number of resistant drugs (p < 0.001) and a higher incidence of resistance to ofloxacin (p = 0.005) in the drug sensitivity test. The treatment success rate was 78.9% in the levofloxacin group and 83.3% in the moxifloxacin group (p = 0.42). Adverse reactions occurred at similar rates in the groups (p = 0.44). Patients in the moxifloxacin group were not more likely to have treatment success than those in the levofloxacin group (adjusted odds ratio, 0.76; 95% confidence interval, 0.24 to 2.43; p = 0.65). CONCLUSIONS: Both levofloxacin and moxifloxacin showed equivalent efficacy for treating MDR-TB.

Anti-tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium tuberculosis isolates.

Background & objectives: Emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis has further complicated the problem of tuberculosis (TB) control. Medicinal plants offer a hope for developing alternate medicines for the treatment of TB. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum and Aloe vera. Methods: Aqueous extracts of leaves of A. indica, A. vasica, bulbs of A. cepa, cloves of A. sativum and pure gel of A. vera leaves, were tested in vitro for their activity against two MDR isolates (DKU-156 and JAL-1236), reference susceptible strain M. tuberculosis H37Rv as well as rapid grower mycobacterial pathogen M. fortuitum (TMC-1529) using Lowenstein Jensen (L-J) medium and colorimetric BacT/ALERT 3D system. Activity in L-J medium was evaluated by percentage inhibition which was calculated by mean reduction in number of colonies on extract containing as compared to extract free controls. Results: Extracts of all the five plants A. indica, A. vasica, A. cepa, A. sativum and A. vera exhibited anti-tuberculosis activity in L-J medium, the proportion of inhibition of these plants extract in respect mentioned above is 95, 32, 37, 72, 32 per cent, respectively for MDR isolate DKU-156 and 68, 86, 79, 72, 85 per cent, respectively for another MDR isolate JAL-1236, while for sensitive M. tuberculosis H37Rv, inhibition was found to be 68, 70, 35, 63 and 41 per cent, at 4 per cent v/v concentration in L-J medium. There was no inhibition against rapid grower M. fortuitum (TMC-1529). In BacT/ALERT also, extracts of these plants showed significant inhibition against M. tuberculosis. Interpretation & conclusions: Our findings showed that all these plants exhibited activity against MDR isolates of M. tuberculosis. While the anti-TB activity of A. vera, A. vasica and A. sativum against MDR isolates confirm earlier results, activity of the extracts of A. indica and A. cepa is reported for the first time. Further studies aimed at isolation and identification of active substances from the extracts which exhibited promising activities, need to be carried out.

Prevalence of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospital-based study.

Background & objective: Extensively drug-resistant tuberculosis (XDR-TB) is a difficult-to-treat form of multidrug-resistant tuberculosis (MDR-TB). High rates of XDR-TB have been reported from India. We sought to ascertain the prevalence of XDR-TB among patients with MDR-TB treated at a tertiary care centre in New Delhi, India. Methods: Case records of patients treated for MDR-TB at the All India Institute of Medical Sciences hospital, New Delhi, between 1997 and 2003 were retrospectively reviewed. All patients underwent a pretreatment drug-susceptibility testing (DST) to first- as well as second-line drugs. XDR-TB was defined as TB caused by bacilli showing resistance to rifampicin and isoniazid in addition to any fluoroquinolone and to at least one of the three following injectable drugs: capreomycin, kanamycin, and amikacin. Results: A total of 211 laboratory-confirmed cases of MDR-TB were reviewed. The mean age of the patients was 33 ± 12 yr. Fifty one (24%) patients were females. All patients were sero-negative for human immunodeficiency virus infection. Five of the 211 MDR-TB patients had XDR-TB. The prevalence of XDR-TB was 2.4 per cent among MDR-TB patients. Interpretation & conclusion: Our results showed that XDR-TB was rare among patients with MDR-TB treated between 1997 and 2003 at our centre. Unreported selection bias might have been responsible for the high prevalence of XDR-TB reported in previous hospital-based studies from India.

Comparative growth pattern of multi drug resistance versus susceptible isolates of Mycobacterium tuberculosis in mice lungs.

Background & objectives: Rise in prevalence of multi-drug resistance (MDR) in tubercle bacilli is a serious cause of concern. As mutations with two house keeping genes rpoB and katG are associated with resistance to two important anti-tubercular drugs rifampicin and isoniazid respectively, there is a need to understand the growth kinetics of organisms with such mutated genes in experimental animals. This study was undertaken to study the growth kinetics of susceptible as well multi-drug resistance Mycobacterium tuberculosis isolates in mice. Methods: Two MDR (having mutations in rpoB and catG) and two drug susceptible isolates of M. tuberculosis along with H37Rv were grown in mice after aerogenic infection. Results: The MDR isolates grew slowly up to 3 wk though the growth was significantly different from sensitive strains. However, after 3 wk, the growth in sensitive as well MDR strains was similar, suggesting that even the mutations in the MDR strains did not have any impact on the growth kinetics. Interpretation & conclusions: The effect of mutations in other parts of these genes need to be studied. Retention of property of MDR strains to establish infection after aerogenic infection has epidemiological significance in terms of the transmission of MDR tuberculosis.

Extensively drug resistance (XDR) tb is not always fatal.

The chance of incidence of XDR TB is on the rise due to improper use of second line anti-tubercular drugs. XDR-TB is very difficult to treat successfully and is often referred to as "virtually untreatable form of TB". We herein report a case of XDR TB confirmed by bacteriological examination in a WHO recognised laboratory who after 12 months of regular treatment improved both clinically and radiologically with sputum smear conversion. To the best of our knowledge, there has been no previous report of any similar case in literature.

Extensively drug-resistant tuberculosis: a case report and literature review

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.

High frequency of resistance to the drugs isoniazid and rifampicin among tuberculosis cases in the city of Cabo de Santo Agostinho, an urban area in Northeastern Brazil

The objective of the present study was to investigate the frequency and risk factors for developing multidrug-resistant tuberculosis in Cabo de Santo Agostinho, PE. This was a prospective study conducted from 2000 to 2003, in which suspected cases were investigated using bacilloscopy and culturing. Out of 232 confirmed cases of tuberculosis, culturing and antibiotic susceptibility tests were performed on 174. Thirty-five of the 174 cultures showed resistance to all drugs. The frequencies of primary and acquired resistance to any drug were 14 percent and 50 percent respectively, while the frequencies of primary and acquired multidrug resistance were 8.3 percent and 40 percent. Previous tuberculosis treatment and abandonment of treatment were risk factors for drug resistance. The high levels of primary and acquired resistance to the combination of isoniazid and rifampicin contributed towards the difficulties in controlling tuberculosis transmission in the city.

O objetivo do presente estudo foi investigar a freqüência e fatores de risco para o desenvolvimento de tuberculose multidroga resistente, na Cidade do Cabo de Santo Agostinho, PE. Este é um estudo prospectivo realizado entre 2000-2003 onde casos suspeitos foram investigados por baciloscopia e cultura. De 232 casos de tuberculose confirmados, 174 tiveram cultura e antibiograma realizados. Trinta e cinco das 174 culturas mostraram resistência a qualquer uma das drogas. A freqüência de resistência primária e adquirida a qualquer droga foi 14 por cento e 50 por cento respectivamente enquanto a freqüência primária e adquirida para multidroga resistência foi 8,3 por cento e 40 por cento. Tratamento prévio para tuberculose ou abandono de tratamento consistiu em fatores de risco para resistência a drogas. Os altos níveis de resistência primária e adquirida a combinação isoniazida e rifampicina contribuem para as dificuldades no controle da transmissão da tuberculose no Cabo.