[Adverse effects of the new tuberculosis treatment regimen recommended by the Brazilian Ministry of Health]. / Efeitos adversos causados pelo novo esquema de tratamento da tuberculose preconizado pelo Ministério da Saúde do Brasil.

OBJECTIVE: To determine the principal adverse effects of the tuberculosis treatment regimen recommended by the Brazilian Ministry of Health. METHODS: A prospective descriptive study involving 79 tuberculosis patients treated at the Clinical Research Center of the Cassiano Antonio Moraes University Hospital, in the city of Vitória, Brazil, between 2003 and 2006. The treatment regimen consisted of isoniazid, rifampicin, pyrazinamide and ethambutol for four months, followed by rifampicin and isoniazid for two months. During the treatment period, the patients were clinically evaluated every week and had a monthly medical visit. RESULTS: The overall incidence of adverse effects was 83.54%. Articular/bone/muscle involvement was the most common, followed by skin involvement (24.94% and 22.09%, respectively). Adverse effects were more common in the second month of treatment (41.59%). Modification of the treatment regimen was unnecessary. One patient required concomitant medication to counter the adverse effects. The cure rate was 100%. CONCLUSIONS: The overall incidence of adverse effects related to the new treatment regimen recommended by the Brazilian Ministry of Health was high. However, none of those effects demanded a change in the regimen, which was effective in the patients evaluated.

Household members and health care workers as supervisors of tuberculosis treatment

Objetivo: Comparar os resultados de cura por tuberculose entre pacientes supervisionados pelo membro familiar e pelo profissional de saúde. Métodos: Estudo de coorte prospectiva de 171 pacientes de Vitória, ES, no período de 2004 a 2007. Cada paciente foi acompanhado por seis meses até a finalização do tratamento. Dos pacientes estudados, 59 pacientes tratados eram supervisionados por um membro familiar e 112 pelos profissionais de saúde. Foram avaliados dados sociodemográficos e clínicos dos pacientes. Diferenças entre os grupos de estudo foram avaliadas utilizando o teste qui-quadrado ou teste t de Student ao nivel de significância de 5 por cento. Resultados: A maioria dos sujeitos do estudo apresentaram bacioscopia positiva e cultura confirmada para tuberculose. Dois pacientes tinham sorologia positiva para HIV. Um número maior de pacientes no grupo supervisionado por profissionais de saúde não eram alfabetizados, comparado com aqueles pacientes do grupo supervisionado por membros familiares (p = 0,01). Todos os pacientes supervisionados por um familiar foram...(AU)Objetivo: Comparar los resultados de cura por tuberculosis entre pacientes supervisados por ele miembro familiar y por el profesional de salud. Métodos: Estudio de cohorte prospectivo de 171 pacientes de Vitória, sureste de Brasil, en el período de 2004 a 2007. Cada paciente fue acompañado por seis meses hasta la finalización del tratamiento. De los pacientes estudiados, 59 pacientes tratados eran supervisados por un miembro familiar y 112 por los profesionales de salud. Fueron evaluados datos sociodemográficos y clínicos de los pacientes. Diferencias entre los grupos de estudio fueron evaluadas utilizando la prueba Chi-cuadrado o prueba t de Student al nivel de significancia de 5 por ciento. Resultados: La mayoría de los sujetos de estudio presentaron bacioscopia positiva y cultivo confirmado...

Efeitos adversos causados pelo novo esquema de tratamento da tuberculose preconizado pelo Ministério da Saúde do Brasil / Adverse effects of the new tuberculosis treatment regimen recommended by the Brazilian Ministry of Health

OBJETIVO: Determinar os principais efeitos adversos causados pelo esquema de tratamento da tuberculose preconizado pelo Ministério da Saúde. MÉTODOS: Estudo descritivo e prospectivo envolvendo 79 pacientes com tuberculose tratados no Centro de Pesquisa Clínica do Hospital Universitário Cassiano Antônio Moraes, no município de Vitória, ES, entre 2003 e 2006. O regime de tratamento consistiu em isoniazida, rifampicina, pirazinamida e etambutol por quatro meses, seguido de rifampicina e isoniazida por dois meses. Durante o tratamento, os pacientes foram clinicamente avaliados todas as semanas e tinham uma visita médica mensal. RESULTADOS: A incidência geral de efeitos adversos foi de 83,54 por cento. O envolvimento articular/ósseo/muscular e o envolvimento cutâneo foram mais frequentes (24,94 por cento e 22,09 por cento, respectivamente). Os eventos adversos foram mais comuns no segundo mês de tratamento (41,59 por cento). Não houve necessidade de modificação do esquema de tratamento. Apenas 1 paciente necessitou de medicação para amenizar os efeitos adversos. A taxa de cura foi de 100 por cento. CONCLUSÕES: Apesar de alta, a incidência de efeitos adversos com o novo esquema de tratamento preconizado pelo Ministério da Saúde não exigiu a modificação do esquema de tratamento, que foi eficaz.

OBJECTIVE: To determine the principal adverse effects of the tuberculosis treatment regimen recommended by the Brazilian Ministry of Health. METHODS: A prospective descriptive study involving 79 tuberculosis patients treated at the Clinical Research Center of the Cassiano Antonio Moraes University Hospital, in the city of Vitória, Brazil, between 2003 and 2006. The treatment regimen consisted of isoniazid, rifampicin, pyrazinamide and ethambutol for four months, followed by rifampicin and isoniazid for two months. During the treatment period, the patients were clinically evaluated every week and had a monthly medical visit. RESULTS: The overall incidence of adverse effects was 83.54 percent. Articular/bone/muscle involvement was the most common, followed by skin involvement (24.94 percent and 22.09 percent, respectively). Adverse effects were more common in the second month of treatment (41.59 percent). Modification of the treatment regimen was unnecessary. One patient required concomitant medication to counter the adverse effects. The cure rate was 100 percent. CONCLUSIONS: The overall incidence of adverse effects related to the new treatment regimen recommended by the Brazilian Ministry of Health was high. However, none of those effects demanded a change in the regimen, which was effective in the patients evaluated.

Household members and health care workers as supervisors of tuberculosis treatment.

OBJECTIVE: To compare tuberculosis cure rates among patients supervised by household members or health care workers. METHODS: Prospective cohort study of 171 patients treated by the program in Vitoria, Southeastern Brazil, from 2004 to 2007. Each patient was followed-up for six months until the end of the treatment. Of the patients studied, a household member supervised 59 patients and healthcare workers supervised 112 patients. Patients' sociodemographic and clinic data were analyzed. Differences between groups were assessed using chi-square test or Student's t-test. Significance level was set at 5%. RESULTS: Most patients had smear positive, culture confirmed pulmonary tuberculosis. Two patients were HIV-positive. There were more illiterate patients in the healthcare-supervised group, in comparison to those supervised by their families (p=0.01). All patients supervised by a household member were cured compared to 90% of the patients supervised by health care workers (p = 0.024). CONCLUSIONS: Successful tuberculosis treatment was more frequent when supervised by household members.

Population pharmacokinetics of linezolid in adults with pulmonary tuberculosis.

Nineteen adults with pulmonary tuberculosis received linezolid (600 mg) once or twice daily in an early bactericidal activity trial. A one-compartment population model produced median values for the absorption rate constant, volume of distribution, and elimination rate constant of 1.5 h(-1), 29.6 liters, and 0.25 h(-1) (once daily) and 2.7 h(-1), 32.1 liters, and 0.15 h(-1) (twice daily). Linezolid administered twice daily produced higher values for free drug area under the concentration-time curve (AUC)/MIC and time above MIC. Both regimens achieved free AUC/MIC ratios > 100. Median times above the MIC for free drug were 100% (twice daily) and 63% (once daily).

Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis.

RATIONALE: Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis. OBJECTIVES: To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis. METHODS: Randomized open label trial. Thirty patients with newly diagnosed smear-positive pulmonary tuberculosis (10 per arm) were assigned to receive isoniazid (300 mg daily) and linezolid (600 mg twice daily or 600 mg once daily) for 7 days. Sputum for quantitative culture was collected for 2 days before and then daily during 7 days of study drug administration. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (early bactericidal activity) and the last 5 days of study drug administration (extended early bactericidal activity). MEASUREMENTS AND MAIN RESULTS: The mean early bactericidal activity of isoniazid (0.67 log10 cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log10 cfu/ml/d, respectively). The extended early bactericidal activity of linezolid between Days 2 and 7 was minimal. CONCLUSIONS: Linezolid has modest early bactericidal activity against rapidly dividing tubercle bacilli in patients with cavitary pulmonary tuberculosis during the first 2 days of administration, but little extended early bactericidal activity. Clinical trial registered with www.clinicaltrials.gov (NCT00396084).

Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis.

The objective of this study was to determine the population pharmacokinetic parameters of levofloxacin, gatifloxacin, and moxifloxacin following multiple oral doses. Twenty-nine patients with tuberculosis at the University Hospital in Vitória, Brazil, participated. Subjects received multiple doses of one drug (levofloxacin, 1,000 mg daily, or gatifloxacin or moxifloxacin, 400 mg daily) as part of a 7-day study of early bactericidal activity. Serum samples were collected over 24 h after the fifth dose and assayed using validated high-performance liquid chromatography assays. Concentration-time data were analyzed using noncompartmental, compartmental, and population methods. The three drugs were well tolerated. Levofloxacin produced the highest maximum plasma concentrations (median, 15.55 microg/ml; gatifloxacin, 4.75 microg/ml; moxifloxacin, 6.13 microg/ml), largest volume of distribution (median, 81 liters; gatifloxacin, 79 liters; moxifloxacin, 63 liters), and longest elimination half-life (median, 7.4 h; gatifloxacin, 5.0 h; moxifloxacin, 6.5 h). A one-compartment model, with or without weight as a covariate, adequately described the data. Postmodeling simulations using median population parameter estimates closely approximated the median values from the original data. Area under the concentration-time curve/MIC ratios for free drug were high. All three quinolones showed favorable pharmacokinetic and pharmacodynamic indices, with the most favorable results in this population being seen with levofloxacin at the comparative doses used.