Efeitos adversos às drogas antituberculose: hepatotoxicidade / Adverse effects to antituberculosis drugs: hepatotoxicity

Objetivo: Verificar a frequência de efeitos adversos em pacientes em uso de drogas antituberculose de primeira linha, além dos fatores de risco associados aos efeitos adversos e à hepatotoxicidade. Métodos: Estudo transversal, envolvendo 196 pacientes portadores de tuberculose em Maceió (AL), de agosto de 2017 a junho de 2018. Os efeitos adversos foram classificados de acordo com o Manual de Recomendações para Controle da Tuberculose de 2011, do Ministério da Saúde, em efeitos menores (queixas gastrintestinais, cutâneos, articulares e neurológicos) e maiores (psicose e hepatotoxicidade). Os fatores de risco avaliados foram: idade superior a 40 anos, etilismo, sexo feminino, anemia, doença hepática anterior, diabetes e infecção por HIV. Resultados: Foram observados efeitos adversos às drogas antituberculose em 85 pacientes (43,4%); destes, 40,8% eram menores e 8,2%, maiores. Os mais frequentes foram distúrbios gastrintestinais (25,5%) e cutâneos (15,3%). Identificaram-se como fatores de risco anemia, diabetes e doença hepática anterior. Hepatotoxicidade foi diagnosticada em 15 pacientes (10,6%), dos quais 80% eram sintomáticos, sendo fatores de risco doença hepática anterior e diabetes. Houve suspensão da terapia em todos os casos de hepatotoxicidade com modificação do esquema em 80% dos casos. Conclusão: Demonstrou-se frequência elevada de efeitos adversos às drogas antituberculose, associada à doença hepática anterior e ao diabetes. A hepatotoxicidade representou o efeito adverso mais grave, responsável pela suspensão e pela adequação do esquema terapêutico.

Objective: To determine the adverse effects frequency in patients on first-line antituberculosis drugs, as well as the risk factors associated with adverse effects and hepatotoxicity. Methods: Cross-sectional study, involving 196 tuberculosis patients in Maceió (AL), from August 2017 to June 2018. Adverse effects were classified according to the Manual de Recomendações para Controle da Tuberculose, of the Brazilian Health Ministry, in minor effects (gastrointestinal, cutaneous, articular, neurologic complaints) and major effects (psychosis and hepatotoxicity). The risk factors evaluated were age over 40 years, alcoholism, female sex, anemia, previous hepatic disease, diabetes, and infection by HIV. Results: Adverse effects to the antituberculosis drugs were observed in 85 patients (43.4%) and, among those, 40.8% were minor and 8.2% were major effects. The most frequent were gastrointestinal (25.5%) and skin (15.3%) disorders. Risk factors were identified as anemia, diabetes, and previous hepatic disease. Hepatotoxicity was diagnosed in 15 patients (10.6%), from which 80% were symptomatic, with previous hepatic disease and diabetes being the risk factors. Therapy was discontinued in all cases of hepatotoxicity with regimen modification in 80% of cases. Conclusion: An elevated frequency of adverse effects to antituberculosis drugs was demonstrated. Hepatotoxicity represented the most severe adverse effect, being responsible for the discontinuation and adaptation of the therapeutic regimen.

Association of adverse drug reaction to anti-tuberculosis medication with quality of life in patients in a tertiary referral hospital

Abstract INTRODUCTION: Adverse drug reactions can develop when using anti-tuberculosis medication, and the effects of the drugs can also significantly hinder the treatment of patients. METHODS: A cross-sectional survey was conducted in 73 patients using two standardized questionnaires and the World Health Organization Quality of Life-Bref. RESULTS: All patients reported the presence of adverse drug reactions, 71.6% of which are minor and 28.3% both major and minor. The global quality of life analysis showed that patients with tuberculosis have a good average (67.3%). CONCLUSIONS: There is an association between quality of life and adverse drug reaction, educational level, and vulnerability.

Drug therapy problems for patients with tuberculosis and HIV/AIDS at a reference hospital / Problemas relacionados ao uso de medicamentos em pacientes com tuberculose e HIV/AIDS em hospital referência

ABSTRACT Objective: To determine the frequency of drug therapy problem in the treatment of patients with tuberculosis and HIV/AIDS. Methods: Data were obtained through a cross-sectional study conducted between September 2015 and December 2016 at a reference hospital in infectious diseases in Belo Horizonte (MG), Brazil. Sociodemographic, clinical, behavioral and pharmacotherapeutic variables were evaluated through a semi-structured questionnaire. Drug-related problems of pharmaceutical care were classified using the Pharmacotherapy Workup method. Factors associated with indication, effectiveness, safety and compliance drug therapy problem were assessed through multiple logistic regression. Results: We evaluated 81 patients, and 80% presented at least one drug therapy problem, with indication and adherence drug therapy problem being the most frequent. The factors associated with drug therapy problem were age, marital status, new case, ethnicity, time of HIV diagnosis and time to treat tuberculosis. Conclusion: The frequency of drug therapy problem in coinfected patients was high and the identification of the main drug therapy problem and associated factors may lead the multiprofessional health team to ensure the use of the most indicated, effective, safe and convenient medicines for the patients clinical condition. Tuberculosis and HIV/AIDS coinfected individuals aged over 40 years are more likely to have drug therapy problems during treatment; in that, the most frequente are those that signal toward need of medication for an untreated health condition and non-compliance to treatment. Thus, older patients, unmarried or married, who have treated tuberculosis before, with a shorter time to tuberculosis treatment and longer time to diagnose HIV/AIDS, should receive special attention and be better followed by a multiprofessional health team because they indicate a higher chance of presenting Problems related to the use of non-adherent drugs.

RESUMO Objetivo: Determinar a frequência de problemas relacionados ao uso de medicamentos no tratamento de pacientes com tuberculose e HIV/AIDS. Métodos: Os dados foram obtidos por estudo transversal realizado entre setembro de 2015 e dezembro de 2016 em hospital referência em doenças infectocontagiosas de Belo Horizonte (MG), Brasil. As variáveis sociodemográficas, clínicas, comportamentais e farmacoterapêuticas foram avaliadas por questionário semiestruturado. Classificaram-se os problemas relacionados ao uso de medicamento empregando o método Pharmacotherapy Workup de atenção farmacêutica. Os fatores associados aos problemas relacionados ao uso de medicamentos de indicação, efetividade, segurança e adesão foram avaliados pela regressão logística múltipla. Resultados: Foram avaliados 81 pacientes, e 80% apresentaram pelo menos um problema relacionado ao uso de medicamentos, sendo os mais frequentes ligados à problemas relacionados ao uso de medicamentos de indicação e adesão. Os fatores associados aos problemas relacionados ao uso de medicamentos foram idade, estado civil, caso novo, etnia, tempo de diagnóstico do HIV e tempo de tratamento da tuberculose. Conclusão: A frequência de problemas relacionados ao uso de medicamentos em pacientes coinfectados foi alta, e a identificação dos principais problemas relacionados ao uso de medicamentos e dos fatores associados aos mesmos pode direcionar a equipe multiprofissional de saúde, para garantir o uso dos medicamentos mais indicados, efetivos, seguros e convenientes para a condição clínica dos pacientes. Os indivíduos coinfectados com tuberculose e HIV/AIDS maiores de 40 anos possuem maior chance de apresentarem problemas relacionados ao uso de medicamentos durante o tratamento, sendo os mais frequentes os que indicam a necessidade de medicamento para condição de saúde não tratada e não adesão ao tratamento. Pacientes mais idosos, solteiros ou não, que já trataram a tuberculose antes, com menor tempo de tratamento de tuberculose e maior tempo de diagnóstico de HIV/AIDS devem ter atenção especial no acompanhamento por uma equipe multiprofissional de saúde por indicarem maior chance de apresentar Problemas Relacionados ao uso de Medicamentos de não adesão à terapia.

Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis / Análise sequencial como ferramenta na detecção da ototoxicidade da amicacina no tratamento da tuberculose multirresistente

ABSTRACT Objective: To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. Methods: This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. Results: We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. Conclusions: The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts.

RESUMO Objetivo: Verificar a detecção precoce de ototoxicidade causada pelo uso de amicacina numa população tratada para tuberculose multirresistente (TBMR) por meio da realização de três testes distintos: audiometria tonal liminar (ATL), audiometria de altas frequências (AAF) e pesquisa de emissões otoacústicas por produto de distorção (EOAPD). Métodos: Estudo longitudinal de coorte prospectiva incluindo pacientes de ambos os sexos, com idade entre 18 e 69 anos, com diagnóstico de TBMR pulmonar e que necessitaram utilizar amicacina por seis meses em seu esquema medicamentoso antituberculose pela primeira vez. A avaliação auditiva foi realizada antes do início do tratamento e depois de dois e seis meses do início do tratamento. A análise dos resultados foi realizada por meio de análise estatística sequencial. Resultados: Foram incluídos 61 pacientes, mas a população final foi constituída de 10 pacientes (7 homens e 3 mulheres), em razão da análise sequencial. Ao se comparar os valores das respostas dos testes com aqueles encontrados na avaliação basal, foram verificadas mudanças nos limiares auditivos compatíveis com ototoxicidade após dois meses de tratamento através da AAF e após seis meses de tratamento através da ATL. Entretanto, essas mudanças não foram verificadas através da pesquisa de EOAPD. Conclusões: Ao se considerar o método estatístico utilizado nessa população, é possível concluir que mudanças nos limiares auditivos foram associadas ao uso da amicacina no período de seis meses por meio de AAF e ATL e que a pesquisa de EOAPD não se mostrou eficiente na identificação dessas mudanças.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

Abstract The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. "Probable reactions" (75%) predominated over "possible reactions" (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs.

Hepatotoxicity induced by antituberculosis drugs among patients coinfected with HIV and tuberculosis / Hepatotoxicidade das drogas antituberculose entre pacientes coinfectados HIV/tuberculose

Hepatotoxicity due to antituberculosis drugs limits treatment in patients coinfected with HIV and tuberculosis. We conducted a case-control study to identify risk factors for hepatotoxicity among patients coinfected with tuberculosis and HIV in two hospitals in Recife, Pernambuco State, Brazil. The sample consisted of 57 patients (36.5% of the total) who developed hepatotoxicity and a control group of 99 patients (63.5% of the total), who did not present this effect. Hepatotoxicity consisted of jaundice or a high concentration of AST/ALT or total bilirubinemia. Multivariate logistic regression showed that a T CD4+ count of < 200cells/mm³ increased the risk of hepatotoxicity by a factor of 1.233 (p < 0.001) and that coinfection with hepatitis B or C virus increased this risk by a factor of 18.187 (p = 0.029). Discharge occurred among 66.1% of the case group (p = 0.026). The absence of hepatotoxicity was a protective factor against death (OR = 0.42; 95%CI: 0.20-0.91). Coinfection with the B and C hepatitis virus and a T CD4+ cell count below 200cells/mm³ were independent risk factors for hepatotoxicity in these patients.

Hepatotoxicidade secundária às drogas antituberculose limita o tratamento em pacientes coinfectados com HIV e tuberculose. Conduzimos estudo caso-controle para identificar fatores de risco para hepatotoxicidade entre pacientes com tuberculose e infecção pelo HIV em dois hospitais de Recife, Pernambuco, Brasil. O grupo caso consistiu de 57 (36,5%) pacientes com hepatotoxicidade e o grupo controle, 99 (63,5%) pacientes que não a apresentaram. Hepatotoxicidade foi definida como icterícia ou alta concentração de ALT/AST ou de bilirrubinemia total. Regressão logística multivariada mostrou que a contagem de linfócitos T CD4+ < 200 células/mm³ aumentou o risco de hepatotoxicidade em 1,233 vezes (p < 0,001), e coinfecção com vírus de hepatite B ou C aumentou o risco em 18,187 (p = 0,029). Alta hospitalar ocorreu em 66,1% dos pacientes do grupo caso (p = 0,026). Ausência de hepatotoxicidade foi fator de proteção para óbito (OR = 0,42; IC: 0,20-0,91). Coinfecção pelos vírus das hepatites B e C e linfócitos T CD4+ abaixo de 200 células/mm³ foram fatores de risco independentes para a hepatotoxicidade nesses pacientes.

Preditores dos desfechos do tratamento da tuberculose / Predictors of tuberculosis treatment outcomes

OBJETIVO: Analisar os desfechos do tratamento da tuberculose e seus preditores. MÉTODOS: Estudo longitudinal de coorte de pacientes com tuberculose tratados entre 2004 e 2006 no Instituto de Pesquisa Evandro Chagas, na cidade do Rio de Janeiro. As razões de risco ajustadas (RRa) dos preditores foram estimadas. RESULTADOS: Foram incluídos 311 pacientes. As taxas de cura, de abandono, de mortalidade e de falha terapêutica foram, respectivamente, 72 por cento, 19 por cento, 6 por cento e 2 por cento. A troca de regime terapêutico por eventos adversos foi necessária em 8 por cento. O alcoolismo (RRa, 0,30), uso do regime estreptomicina+etambutol+ofloxacina (SEO; RRa, 0,32), infecção por HIV sem tratamento antirretroviral (TARV; RRa, 0,36) e o uso do regime rifampicina+isoniazida+pirazinamida+etambutol (RRa, 0,58) reduziram a probabilidade de cura. A faixa etária mais jovem (RRa, 3,84) e o alcoolismo (RRa, 1,76) aumentaram a probabilidade do abandono. Não foi possível determinar as RRa para os demais desfechos devido a suas baixas prevalências. Entretanto, medidas do risco relativo (RR) identificaram os seguintes potenciais preditores do óbito: uso de esquema SEO (RR, 11,43), infecção pelo HIV sem TARV (RR, 9,64), forma clínica disseminada (RR, 9,09), ausência de confirmação bacteriológica (RR, 4,00), diabetes mellitus (RR, 3,94) e comportamento homo/bissexual (RR, 2,97). A baixa renda (RR, 11,70) foi potencial preditor para falha terapêutica, ao passo que infecção pelo HIV com uso de TARV (RR, 2,46) e forma clínica disseminada (RR, 3,57) foram potenciais preditores para troca do esquema por evento adverso. CONCLUSÕES: O esquema SEO deve ser utilizado transitoriamente quando possível. Os dados confirmam a importância de TARV e sugerem a necessidade de seu início precoce.

OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors. METHODS: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72 percent, 19 percent, 2 percent, and 6 percent, respectively. Changes in the treatment regimen due to adverse events occurred in 8 percent. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). CONCLUSIONS: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.

Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment.

Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity / Hepatotoxicidade induzida pelos tuberculostáticos: comparação em pacientes com e sem soropositividade para o vírus da imunodeficiência humana

INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77 percent and 46 percent, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4 percent) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.

INTRODUÇÃO: Avaliou-se a prevalência e os fatores de risco para hepatotoxicidade aos tuberculostáticos em pacientes HIV positivos e controles. MÉTODOS: Selecionou-se 162 pacientes com tuberculose, tratados com rifampicina, isoniazida e pirazinamida, na faixa etária de 18 a 80 anos, internados em hospital público no Brasil, entre 2005 e 2007. Eles foram divididos em dois grupos: 30 infectados pelo HIV e 132 controles. Adotou-se três definições para hepatotoxicidade: I) aumento de três vezes no valor inferior normal da alanina-aminotransferase (ALT); II) aumento de três vezes no valor superior normal (VSN) da ALT; III) aumento de três vezes no VSN da ALT e duas vezes no VSN da bilirrubina total. RESULTADOS: Nos grupos com e sem infecção pelo HIV, a frequência de hepatotoxicidade I foi de 77 por cento e 46 por cento, respectivamente (p<0,01). Para as definições II e III a frequência de hepatotoxicidade não diferiu entre os grupos estudados. De 17 pacientes com hepatotoxicidade induzida por droga (definição III), três não apresentaram sintomas e o tratamento foi mantido sem intercorrências. Oito (36,4 por cento) de 22 indivíduos apresentaram efeitos colaterais e interromperam o tratamento, mas não apresentavam hepatotoxicidade pela definição III. O abuso de álcool associou-se à hepatotoxicidade apenas para a definição I. CONCLUSÕES: Na dependência da definição escolhida, a infecção pelo HIV pode ou não associar-se à hepatotoxicidade. Foi grande o impacto que pequenas alterações na definição de hepatotoxicidade tiveram nos resultados. Nenhuma morte associou-se ao uso de tuberculostáticos. O surgimento de sintomas não pôde ser atribuído aos tuberculostáticos em um terço dos casos.

Effectiveness and safety of isoniazid chemoprophylaxis for HIV-1 infected patients from Rio de Janeiro

The clinical and epidemiological characteristics, adverse events, treatment adherence and effectiveness of isoniazid chemoprophylaxis were analyzed in a cohort of 138 tuberculosis/HIV-coinfected patients. An open, non-randomized, pragmatic prophylactic trial was conducted on adult patients with a normal chest X-ray and positive tuberculin skin test (> 5 mm) who received isoniazid chemoprophylaxis (300 mg/day) for six months. The mean of follow up was 2.8 years (SD 1.3). Adherence to chemoprophylaxis was 87.7 percent (121/138). Only one patient presented tuberculosis after the end of chemoprophylaxis, corresponding to 0.3 cases per 100 persons per year. The relative risk of some adverse effects was 4.6 times higher (95 percent CI: 1.9-11.5) in patients with positive anti-HCV serology (4/9, 44.4 percent) compared to those with negative serology (12/129, 9.6 percent) (p = 0.002). This study provides evidence regarding the effectiveness and safety of a short and self-administered isoniazid regimen. We recommend the implementation of this routine by health service practitioners.

Efeitos adversos no tratamento da tuberculose: experiência em serviço ambulatorial de um hospital-escola na cidade de São Paulo / Adverse effects of tuberculosis treatment: experience at an outpatient clinic of a teaching hospital in the city of São Paulo, Brazil

OBJETIVOS: Verificar a freqüência de efeitos adversos com o uso do Esquema I para tratamento da tuberculose e a necessidade de alterações no tratamento devido a esses efeitos. MÉTODOS: Foi feita uma análise retrospectiva de 329 prontuários de pacientes que foram tratados com o Esquema I e receberam alta por cura entre março de 2000 e abril de 2006 no Ambulatório de Tuberculose da Clínica de Pneumologia da Santa Casa de Misericórdia de São Paulo. Foram analisados os dados referentes aos efeitos adversos, época de seu aparecimento e modificações do esquema de tratamento subseqüentes. RESULTADOS: Foram incluídos 297 pacientes, e 146 (49,1 por cento) apresentaram um ou mais efeitos adversos relacionados às drogas antituberculose. A freqüência dos efeitos colaterais menores foi de 41,1 por cento, e a dos efeitos maiores foi de 12,8 por cento. Os efeitos relacionados ao trato gastrointestinal (40,3 por cento) e pele (22,1 por cento) foram os mais freqüentes. Os efeitos adversos foram mais freqüentes nos primeiros dois meses de tratamento (58,4 por cento). Houve necessidade de modificação do esquema de tratamento em 11 casos (3,7 por cento do total). A hepatite induzida por medicamentos foi o efeito colateral que mais exigiu modificações. CONCLUSÕES: A freqüência de efeitos adversos relacionados ao tratamento da tuberculose com o Esquema I foi de 49,1 por cento neste grupo de pacientes. Entretanto, na maioria dos casos, não houve necessidade da modificação do esquema de tratamento devido aos efeitos adversos.

OBJECTIVES: To determine the frequency of adverse effects related to the use of the tuberculosis treatment regimen designated Regimen I and the need for regimen alterations due to these effects. METHODS: A retrospective analysis of 329 medical charts of patients who were treated with Regimen I and discharged after cure between March 2000 and April 2006 was carried out at the Tuberculosis Outpatient Clinic, Department of Pulmonology of the Santa Casa de Misericórdia de São Paulo Hospital in the city of São Paulo, Brazil. Adverse effects and the timing of their appearance, as well as subsequent modifications in the treatment regimen, were investigated. RESULTS: We included 297 patients, 146 (49.1 percent) of whom presented one or more adverse effects related to antituberculosis medications. The frequency of minor side effects was 41.1 percent, and that of major side effects was 12.8 percent. The most common reactions were those involving the gastrointestinal tract (40.3 percent) and the skin (22.1 percent). Adverse effects were more common in the first and second months of treatment (58.4 percent). Modification of the treatment regimen was necessary in 11 cases (3.7 percent of the total sample). Drug-induced hepatitis was the adverse effect that demanded the most regimen changes. CONCLUSIONS: In this group of patients, the frequency of adverse effects related to treatment with Regimen I was 49.1 percent. However, in most of the cases, it was not necessary to modify the treatment regimen due to side effects.

Análise do tratamento da tuberculose pulmonar em idosos de um hospital universitário do Rio de Janeiro, RJ, Brasil / Analysis of the treatment of pulmonary tuberculosis in elderly patients at a university hospital in Rio de Janeiro, Brazil

OBJETIVOS: Descrever os aspectos clínicos e terapêuticos da tuberculose pulmonar e comparar os efeitos adversos e resultados do tratamento entre idosos e não idosos. MÉTODOS: Foi realizado um estudo caso-controle com 117 indivíduos idosos (acima de 60 anos) e 464 não idosos (15-49 anos) portadores de tuberculose pulmonar atendidos no Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro no período de 1980 a 1996. RESULTADOS: No grupo de idosos, houve associação entre diabetes mellitus (OR = 3,98; IC95 por cento = 2,07-7,65; p = 0,001), doenças pulmonares (OR = 7,24; IC95 por cento = 3,64-14,46; p = 0,001) e cardiovasculares (OR = 5,86; IC95 por cento = 2.88-11.95; p = 0,001). O tabagismo (OR = 2,07; IC95 por cento = 1,26-3,42; p = 0,002) e o etilismo (OR = 1,63; IC95 por cento = 1,01-2,68; p = 0,041) também foram mais freqüentes neste grupo. O tratamento levou a freqüentes reações adversas nos idosos (OR = 1,62; IC95 por cento = 1,04-2,54; p = 0,024), principalmente de origem gastrintestinal (OR = 1,64; IC95 por cento = 1,01-2,77; p = 0,047), e sua eficácia foi menor neste grupo: apenas 51 por cento de cura e 24 por cento de óbitos. O abandono do tratamento foi elevado nos dois grupos, em torno de 23 por cento. CONCLUSÕES: As reações adversas e o resultado do tratamento foram piores nos idosos, com maior freqüência de complicações e letalidade, devido a uma maior toxicidade farmacológica e a uma maior prevalência de doenças associadas neste grupo etário.

OBJECTIVE: To describe the clinical and therapeutic aspects of pulmonary tuberculosis and compare the adverse effects of the treatment and its outcome in elderly and nonelderly patients. METHODS: This was a case-control study of 117 elderly individuals (over the age of 60 years) and 464 nonelderly individuals (aged 15-49 years). All subjects presented pulmonary tuberculosis that had been diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 1980 and 1996. RESULTS: In the elderly group, pulmonary tuberculosis was found to be correlated with diabetes (OR = 3.98; 95 percent CI = 2.07-7.65; p = 0.001), lung disease (OR = 7.24; 95 percent CI = 3.64-14.46; p = 0.001) and heart disease (OR = 5.86; 95 percent CI = 2.88-11.95; p = 0.001). Smoking (OR = 2.07; 95 percent CI = 1.26-3.42; p = 0.002) and alcohol abuse (OR = 1.63; 95 percent CI = 1.01-2.68; p = 0.041) were also more common in the elderly group. In the elderly group, the treatment more frequently resulted in adverse reactions (OR = 1.62; 95 percent CI = 1.04-2.54; p = 0.024), especially gastrointestinal reactions (OR = 1.64; 95 percent CI = 1.01-2.77; p = 0.047), and treatment efficacy was lower: cure rate, 51 percent; mortality rate, 24 percent. Treatment adherence was low (approximately 77 percent) in both groups. CONCLUSIONS: In the elderly group, adverse reactions were more common, treatment outcomes were less favorable, there was a greater frequency of clinical complications and deaths related to drug toxicity, and the prevalence of concomitant diseases was higher.

Significación clínico-epidemiológica de la hepatotoxicidad por fármacos en la consulta hepatológica / Clinic-epidemiological significance of the hepatotoxicity by pharmaceutical preparations in the liver consultation

Se analizaron los datos epidemiológicos y clínico-evolutivos de la hepatotoxicidad por fármacos en una experiencia de 10 años (1988-1998) de nuestra Unidad de Hígado, que incluye 10342 historias clínicas de registro prospectivo. La prevalencia en este material fué de 5,6 por ciento, con ligero predominio femenino (1.4:1) y en mayores de 40 años; más del 50 por ciento ingirieron 2 o más fármacos. Predominaron las formas agudas (91.4 por ciento) e ictéricas (60.4 por ciento) con manifestaciones sistémicas de hipersensibilidad en 29.3 por ciento, el 4.5 por ciento de las formas agudas se presentaron como fallo hepático agudo severo, con necesidad de transplante hepático en un caso. los 4 casos de hepatitis crónica presentaron evolución a la cirrosis en un caso, y un caso de colestasis con ductopenia (CBP-simil) evolucionó favorablemente en 19 semanas, recibiendo ácido ursode-soxicólico 10 mg/k/día. Seis fármacos representaron el 53.4 por ciento de los casos: anticonceptivos orales, isoniacida, sulfamidas, clorpropamida, carbamacepina y amiodarona.