Adverse reactions to antituberculosis drugs presenting as DRESS syndrome and acute liver failure

Drug induced liver injury (DILI) can be can be triggered by many medications including antituberculosis drugs. We present the case of a 37-year-old woman with a smear- positive pulmonary tuberculosis who started treatment with first-line antituberculosis drugs and 4 weeks later presented jaundice, somnolence and a morbilliform generalized rash with progressive neurologic deterioration which had a fatal outcome. Antituberculosis drugs can cause DILI in 2 to 28% of patients and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) in 1.2%. Acute liver failure (ALF) can occur in 35% of patients with DILI with an overall mortality of 9.7%. If the ALF is unresponsive to medical treatment, liver transplantation has shown promising results and can avoid progression of complications. DILI can be a serious medical condition in patients receiving antituberculosis drugs. If ALF develops and is unresponsive to medical treatment, liver transplantation should be considered as the treatment of choice.

La injuria hepática inducida por fármacos (IHIF) puede ser desencadenado por varios medicamentos incluyendo fármacos anti tuberculosos. Presentamos el caso de una paciente mujer de 37 años con un frotis positivo para tuberculosis pulmonar quien inició tratamiento de primera línea y 4 semanas después, presentó ictericia, somnolencia y un exantema generalizado de tipo morbiliforme con deterioro neurológico progresivo y un desenlace fatal. Los fármacos anti tuberculosos pueden producir injuria inducida por fármacos en 2 a 28% de pacientes y síndrome de DRESS (reacción de sensibilidad a medicamentos con eosinofilia y síntomas sistémicos) en 1,2%. La falla hepática aguda (FHA) en pacientes con injuria hepática inducida por fármacos, puede presentarse en un 35% con una mortalidad del 9,7%. Si la FHA no responde a tratamiento médico, el trasplante hepático ha mostrado resultados positivos y evita la progresión de complicaciones. La IHIF puede ser una condición médica grave en pacientes que reciben medicamentos antituberculosos. Si se desencadena una FHA y no responde a tratamiento médico, debe considerarse con urgencia la posibilidad de trasplante hepático.

Current status of antimicrobial therapy for tuberculosis / 中国基层医药

Multidrug-resistant tuberculosis has a long treatment course and a low sputum-negative conversion rate, which have always been the treatment challenges. New drugs for multidrug-resistant tuberculosis have been constantly explored by scholars worldwide. Multiple antibacterial drugs have been found to have the therapeutic effects on multidrug-resistant tuberculosis. Treatment options that can shorten the duration of tuberculosis are also being explored. Addition of certain antibacterial drugs has been found to shorten the duration of tuberculosis. This paper reviews the effects of antibacterial drugs against tuberculosis.

Drug induced liver injury: East versus West - a systematic review and meta-analysis.

Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize.

Causal association of antibiotic use and resistant tuberculosis infection: Casecontrol meta-analysis / Factores de riesgo para la infección por tuberculosis resistente: Metanálisis de estudios de casos y controles

BACKGROUND: In the world scientific literature, analytical research on tuberculosis has not been meta-analyzed. The objective of this study was to identify risk factors for tuberculosis infection with drug resistance and meta-analyze the causal relationship of prior antibiotic use. METHODS: Systematic review with meta-analysis of case-control studies, in five databases. An ex ante, exhaustive and reproducible protocol of search and selection was applied; with criteria of inclusion, exclusion and evaluation of methodological quality. Were performed a qualitative and quantitative synthesis of the articles that evaluated the previous consumption of antibiotics. The PRISMA guide applied and a meta-analysis of random effects was performed for the odds ratios, with analysis of Galbraith, Funelt Plot, Forest plot and sensitivity analysis. RESULTS: We included 36 articles for the qualitative synthesis and 16 in the meta-analysis. We found a wide heterogeneity in the risk factors that include sociodemographic characteristics such as age, sex, schooling, occupation and prison; Clinics as contact with infected, absence of BCG vaccine, hospitalization, chronic comorbidities, malnutrition, HIV coinfection; And microbiological variables such as infection by Beijing genotype and therapeutic adherence. In the studies that evaluated previous consumption of antibiotic, 1880 cases and 5291 controls were studied, most with moderate or low methodological quality, with a combined measure that shows that the odds of developing resistance in patients with previous antibiotic use are 12 (95% = 6.0-23.7) times found for the non-exposed, in the meta-regression the odds were 16.6 (95% CI = 4.1-67.8) for the moderate quality studies and 5.0 (95% CI = 2.9, 8.7) for those with high methodological quality. CONCLUSIONS: This meta-analysis revealed a strong causal association between the prior use of anti-tuberculosis antibiotics and drug-resistant Micobacterium tuberculosis infection.

OBJETIVO: En la literatura científica mundial no se han metanalizado investigaciones analíticas en tuberculosis. El objetivo del estudio fue identificar factores de riesgo para la infección por tuberculosis con resistencia a medicamentos y meta-analizar la relación causal del uso previo de antibióticos. METODOS: Revisión sistemática con metanálisis de estudios de casos y controles, en cinco bases de datos. Se aplicó un protocolo de búsqueda y selección ex ante, exhaustivo y reproducible; con criterios de inclusión, exclusión y evaluación de calidad metodológica. Se realizó síntesis cualitativa de los artículos y cuantitativa para los estudios que evaluaron el consumo previo de antibióticos. Se cumplió la guía PRISMA y se realizó metanálisis de efectos aleatorios para las razones de odds, con análisis de Galbraith, Funelt Plot, Forest plot y análisis de sensibilidad. RESULTADOS: Se incluyeron 36 artículos para la síntesis cualitativa y 16 en el metanálisis. Se encontró una amplia heterogeneidad en los factores de riesgo que incluyen características sociodemográficas como edad, sexo, escolaridad, ocupación y estar en prisión; clínicas como contacto con infectados, ausencia vacuna con BCG, hospitalización, comorbilidades crónicas, malnutrición, coinfección por VIH; y variables microbiológicas como infección por genotipo Beijing y adherencia terapéutica. En los estudios que evaluaron el consumo de antibióticos se estudiaron 1880 casos y 5291 controles, la mayoría con moderada o baja calidad metodológica, con una medida combinada que evidencia que la odds de desarrollar resistencia en quienes presentan consumo previo de antibióticos es 12 (IC95%= 6,0-23,7) veces la hallada para los no expuestos, en la meta-regresión la odds fue 16,6 (IC95%=4,1-67,8) para los estudios de calidad moderada y 5,0 (IC95%=2,9-8,7) para los de alta calidad metodológica. CONCLUSIONES: En este metanálisis se evidenció la asociación causal fuerte entre el uso previo de antibióticos antituberculosos y la infección por Micobacterium tuberculosis resistente a los fármacos.

Epidemiologia global de pacientes com tuberculose multidrogarresistente (MDR-TB) e extensivamente resistente (XDR-TB) / Global epidemiology of patients with multidrugresistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB)

A tuberculose multidrogarresistente (MDR-TB) e a tuberculose extensivamente resistente (XDR-TB), levantam preocupações pelo grande número de casos, especialmente na África, Ásia e Europa, e pela taxa de sucesso ainda baixa no tratamento, atingindo 54% para MDR-TB e 30% para XDR-TB. O objetivo do presente estudo é relatar as diferentes realidades epidemiológicas dos doentes com MDR-TB e XDR-TB em diferentes partes do mundo. Foram revisados artigos da última década nas bases científicas disponíveis. Os estudos mostraram que a maioria das pessoas afetadas pela MDR-TB são do sexo masculino, migrantes ou imigrantes, que já haviam sido tratados anteriormente. Descrevemos que o tratamento da tuberculose (TB) usualmente resulta em cura, mas também pode levar à seleção dos bacilos mais resistentes. Mostramos que o surgimento de cepas resistentes na TB se deve ao tratamento inadequado de formas mais simples de TB, com cepas resultantes de manejo difícil e que as populações vulneráveis são as mais afetadas. Salientamos que o abandono do tratamento é fator que comumente origina esse problema complexo da doença e elencamos os genes de resistência mais estudados. (AU)

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) raise concerns for their great number of cases, especially in Africa, Asia and Europe, and for their still low treatment success rate, reaching 54% for MDR-TB and 30% for XDR-TB. The objective of this study is to report the epidemiological situation of patients with MDR-TB and XDR-TB in different parts of the world. Articles published in the last decade were collected from available scientific databases and reviewed. The studies showed that most of those affected by MDR-TB are male, migrants or immigrants, and had been previously treated for tuberculosis (TB). We report that TB treatment usually ends in cure, but may also lead to selection of the most resistant bacilli. We show that the emergence of resistant strains in TB is due to inappropriate treatment of simpler forms of TB, resulting in strains of difficult management, and that the most vulnerable populations are the most affected. We emphasize that treatment dropout is the factor most commonly associated with this complicated issue, and also list the most studied multidrug resistance genes. (AU)

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.

Empirical treatment of highly suspected nontuberculous mycobacteria infections following aesthetic procedures.

BACKGROUND: Infection caused by nontuberculous mycobacteria (NTM) has been increasing. Awareness of this infection is crucial yet problematic. Delayed management may lead to destructive results. We empirically treated a series of patients with clinical suspicion of NTM infection prior to the identification of the pathogen. METHODS: A total of 12 patients who developed surgical site infections between January 2011 and February 2014 were reviewed. Patients with a skin and subcutaneous infection resistant to standard management over two weeks, and previous history of aesthetic procedures within three months were regarded as highly suspected of having an NTM infection. A variety of diagnostic modalities were examined simultaneously, along with starting empirical treatment including a combination of clarithromycin and moxifloxacin, and surgical debridement. RESULTS: All wounds healed completely within 4 weeks. The mean follow-up duration was 7.2 months, and none of the patients developed relapse. Specific NTM pathogens were identified in six patients. Eight patients showed caseating granuloma implying an NTM infection. One patient showed an uncommon Stenotrophomonas infection, which was successfully treated. Three patients had no evidence of a pathogen despite repeated microbial tests. Complications such as scarring, pigmentation, and disfigurement were common in all the patients. CONCLUSIONS: NTM should be considered in the differential diagnosis of an unusual skin and soft-tissue infection. We propose an empirical regimen of clarithromycin and moxifloxacin as an efficient treatment option for an NTM infection.

Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB.

BACKGROUND: Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to nine months has 60% to 90% protective efficacy, but the treatment period is long, liver toxicity is a problem, and completion rates outside trials are only around 50%. Rifampicin or rifamycin-combination treatments are shorter and may result in higher completion rates. OBJECTIVES: To compare the effects of rifampicin monotherapy or rifamycin-combination therapy versus INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; clinical trials registries; regional databases; conference proceedings; and references, without language restrictions to December 2012; and contacted experts for relevant published, unpublished and ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) of HIV-negative adults and children at risk of active TB treated with rifampicin, or rifamycin-combination therapy with or without INH (any dose or duration), compared with INH for six to nine months. DATA COLLECTION AND ANALYSIS: At least two authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks (RRs) with their 95% confidence intervals (CIs), using a random-effects model if heterogeneity was significant. We assessed overall evidence quality using the GRADE approach. MAIN RESULTS: Ten trials are included, enrolling 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years. Rifampicin (three/four months) vs. INH (six months) Five trials published between 1992 to 2012 compared these regimens, and one small 1992 trial in adults with silicosis did not detect a difference in the occurrence of TB over five years of follow up (one trial, 312 participants; very low quality evidence). However, more people in these trials completed the shorter course (RR 1.19, 95% CI 1.01 to 1.30; five trials, 1768 participants; moderate quality evidence). Treatment-limiting adverse events were not significantly different (four trials, 1674 participants; very low quality evidence), but rifampicin caused less hepatotoxicity (RR 0.12, 95% CI 0.05 to 0.30; four trials, 1674 participants; moderate quality evidence). Rifampicin plus INH (three months) vs. INH (six months) The 1992 silicosis trial did not detect a difference between people receiving rifampicin plus INH compared to INH alone for occurrence of active TB (one trial, 328 participants; very low quality evidence). Adherence was similar in this and a 1998 trial in people without silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence). Rifampicin plus pyrazinamide (two months) vs. INH (six months) Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving rifampicin plus pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed rifapentine plus INH (three months) vs. daily, self-administered INH (nine months) A large trial conducted from 2001 to 2008 among close contacts of TB in the USA, Canada, Brazil and Spain found directly observed weekly treatment to be non-inferior to nine months self-administered INH for the incidence of active TB (0.2% vs 0.4%, RR 0.44, 95% CI 0.18 to 1.07, one trial, 7731 participants; moderate quality evidence). The directly-observed, shorter regimen had higher treatment completion (82% vs 69%, RR 1.19, 95% CI 1.16 to 1.22, moderate quality evidence), and less hepatotoxicity (0.4% versus 2.4%; RR 0.16, 95% CI 0.10 to 0.27; high quality evidence), though treatment-limiting adverse events were more frequent (4.9% versus 3.7%; RR 1.32, 95% CI 1.07 to 1.64 moderate quality evidence) AUTHORS' CONCLUSIONS: Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens. Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens. Rifampicin combined with pyrazinamide is associated with more adverse events. A weekly regimen of rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.

Empirical Treatment of Highly Suspected Nontuberculous Mycobacteria Infections Following Aesthetic Procedures

BACKGROUND: Infection caused by nontuberculous mycobacteria (NTM) has been increasing. Awareness of this infection is crucial yet problematic. Delayed management may lead to destructive results. We empirically treated a series of patients with clinical suspicion of NTM infection prior to the identification of the pathogen. METHODS: A total of 12 patients who developed surgical site infections between January 2011 and February 2014 were reviewed. Patients with a skin and subcutaneous infection resistant to standard management over two weeks, and previous history of aesthetic procedures within three months were regarded as highly suspected of having an NTM infection. A variety of diagnostic modalities were examined simultaneously, along with starting empirical treatment including a combination of clarithromycin and moxifloxacin, and surgical debridement. RESULTS: All wounds healed completely within 4 weeks. The mean follow-up duration was 7.2 months, and none of the patients developed relapse. Specific NTM pathogens were identified in six patients. Eight patients showed caseating granuloma implying an NTM infection. One patient showed an uncommon Stenotrophomonas infection, which was successfully treated. Three patients had no evidence of a pathogen despite repeated microbial tests. Complications such as scarring, pigmentation, and disfigurement were common in all the patients. CONCLUSIONS: NTM should be considered in the differential diagnosis of an unusual skin and soft-tissue infection. We propose an empirical regimen of clarithromycin and moxifloxacin as an efficient treatment option for an NTM infection.

Vigilancia de la resistencia a los fármacos antituberculosos en Cuba, 2000–2009 / Surveillance of resistance to antitubercular drugs in Cuba, 2000–2009

Objetivo. Determinar la prevalencia de la resistencia a los fármacos antituberculosos en Cuba en el decenio 2000–2009. Métodos. Se realizó un estudio prospectivo longitudinal. El universo de trabajo estuvo constituido por un total de 2 285 aislamientos de Mycobacterium tuberculosis obtenidos de todo el país en el período comprendido entre el 1 de enero de 2000 y el 31 de diciembre de 2009. Se empleó el método de las proporciones en medio Löwenstein-Jensen con los fármacos de primera línea: isoniazida, estreptomicina, etambutol y rifampicina. Resultados. La resistencia entre los casos nuevos y los pacientes con antecedente de tratamiento previo fue de 8,5% y 37,0%, respectivamente; para estas mismas categorías de caso, la multirresistencia fue de 0,4% y 8,8%, respectivamente. Conclusiones. El presente estudio muestra baja prevalencia de cepas multirresistentes en Cuba. Estos resultados reflejan los avances logrados por el programa nacional de control, que trabaja en la actualidad hacia la eliminación de la tuberculosis como problema de salud pública en el país.

Objective. Determine the prevalence of resistance to antitubercular drugs in Cuba in the 2000–2009 decade. Methods. A prospective longitudinal study was conducted. The sample group consisted of 2 285 Mycobacterium tuberculosis isolates obtained from throughout the country in the period from 1 January 2000 to 31 December 2009. The proportion method was used in Löwenstein-Jensen media with the first-line drugs: isoniazid, streptomycin, ethambutol, and rifampicin. Results. In the new cases and patients with a history of previous treatment, resistance was 8.5% and 37.0%, respectively. In these case categories, multidrug resistance was 0.4% and 8.8%, respectively. Conclusions. This study shows low prevalence of multidrug-resistant strains in Cuba. The results reflect the progress made by the national control program, which is currently working on the elimination of tuberculosis as a public health problem in the country.

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha / Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 1: first-line drugs

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Revisamos sucintamente o novo tratamento farmacológico da tuberculose introduzido pelo Ministério da Saúde do Brasil em 2009 e mostramos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no esquema básico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal. Também descrevemos os mecanismos pelos quais as interações das drogas antituberculose do esquema básico podem causar hepatite medicamentosa e as possíveis alternativas nessa situação.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen can cause druginduced hepatitis, and we discuss the alternatives in this situation.

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha / Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 2: second line drugs

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Descrevemos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no tratamento da tuberculose multidroga resistente (aminoglicosídeos, fluoroquinolonas, cicloserina/terizidona, etionamida, capreomicina e ácido para-aminossalicílico). Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal.

The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid). We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

Tuberculose ocular / Ocular tuberculosis

Relato de quatro casos de tuberculose ocular presumida, com comprometimento do segmento posterior em três destes casos. Nos dois primeiros casos, relata-se comprometimento do segmento anterior do olho e antecedente de tuberculose, em um caso sistêmica e no outro ocular. No terceiro caso, paciente apresenta lesão coriorretiniana no olho esquerdo. No quarto caso, descrita lesão serpiginosa-like. Os pacientes evoluíram favoravelmente com o tratamento específico. As lesões oculares da tuberculose são diversas e devemos continuar atentos a esta enfermidade.

Report of four cases of presumed ocular tuberculosis, with involvement of the posterior segment in tree cases. In the first and second case, report anterior involvement of the eye and antecedent of tuberculosis, in a systemic case and the other ocular. In the third case, patient presents coriorretiniana lesion in the left eye. In the fourth case, report lesion serpiginosa-like.The patients under-went the treatment for tuberculosis. The ocular lesions of the tuberculosis are polymorphic and we must be aware of this disease.

Primary and acquired drug resistance in childhood tuberculosis

This study determined the resistance pattern of Mycobacterium tuberculosis to 4 first-line anti-tuberculosis drugs in children with pulmonary tuberculosis at the Iranian National Research Institute of Tuberculosis and Lung Diseases from 1999 to 2004. There were 350 children with positive cultures over the study period: 7 [2%] were resistant to at least one of the 4 anti-tuberculosis drugs. Primary resistance was detected in 4 cases and secondary resistance in 3 cases. Most cases [6] were among Afghan refugees. Resistance to rifampicin both in primary and secondary resistances was high, showing that children in the Islamic Republic of Iran face the threat of drug-resistant tuberculosis transmission

Diagnosis and Treatment of Nontuberculous Mycobacterial Pulmonary Diseases: A Korean Perspective

The incidence of pulmonary disease caused by nontuberculous mycobacteria (NTM) appears to be increasing worldwide. In Korea, M. avium complex and M. abscessus account for most of the pathogens encountered, whilst M. kansasii is a relatively uncommon cause of NTM pulmonary diseases. NTM pulmonary disease is highly complex in terms of its clinical presentation and management. Because its clinical features are indistinguishable from those of pulmonary tuberculosis and NTMs are ubiquitous in the environment, the isolation and identification of causative organisms are mandatory for diagnosis, and some specific diagnostic criteria have been proposed. The treatment of NTM pulmonary disease depends on the infecting species, but decisions concerning the institution of treatment are never easy. Treatment requires the use of multiple drugs for 18 to 24 months. Thus, treatment is expensive, often has significant side effects, and is frequently not curative. Therefore, clinicians should be confident that there is sufficient pathology to warrant prolonged, multidrug treatment regimens. In all of the situations, outcomes can be best optimized only when clinicians, radiologists, and laboratories work cooperatively.