Concentrations of rifampicin in pre-dose samples in patients with pulmonary tuberculosis

ABSTRACT Rifampicin is used in both phases of treatment for tuberculosis. In chronic use, the short half-life and the self-induction of metabolism can decrease the levels of the drug below the minimal inhibitory concentration. The aim of the study was to investigate whether plasma concentrations of rifampicin are sustained above 0.5 µg/mL in patients with tuberculosis using 600 mg/day. Rifampicin was measured in plasma by high-performance liquid chromatography and a sputum smear microscopy was performed in all days of the study. A total of 44 male patients completed the study. On days 31, 61 and 91, the mean plasma concentrations of rifampicin were 0.6 (0.5) µg/mL, 0.55 (0.5) µg/mL and 0.46 (0.4) µg/mL. There was a high variation of rifampicin levels leading to a high percentage of samples with concentrations below 0.5 µg/mL. There was no significant association between the frequency of samples with drug levels below 0.5 µg/mL with the conversion of the sputum microscopy. These data suggest that pre-doses samples offer limited information on the exposure of M. tuberculosis to rifampicin.

Effect of Indacaterol on Cough and Phlegm in Chronic Obstructive Pulmonary Disease Patients: A Meta-Analysis of Five Randomized Controlled Trials

We investigated the effects of indacaterol on cough and phlegm in patients with stable chronic obstructive pulmonary disease (COPD). We performed a meta-analysis with five randomized controlled trials (RCTs) of indacaterol in stable COPD patients. The symptom severity was defined using the St. George's Respiratory Questionnaire (SGRQ). We analyzed patients treated with 150 microg (n = 945) and 300 microg (n = 832) out of 3,325 patients who completed the SGRQ from five RCTs. After a 12-week treatment of 150 microg indacaterol, cough improvement was reported in 36.5% (316/866) of patients treated with indacaterol vs. 32.2% (259/804) patients treated with placebo (Relative Ratio [RR], 1.13; 95% confidence interval [CI], 0.99-1.29). Phlegm improvement was reported in 31.0% (247/798) of patients treated with indacaterol vs. 30.6% (225/736) of patients treated with placebo (RR, 1.01; 95% CI, 0.87-1.18). Dyspnea improvement was reported in 39.5% (324/820) of patients treated with indacaterol vs. 31.5% (237/753) patients treated with placebo (RR, 1.33; 95% CI, 1.03-1.71; P = 0.001, I2 = 55.1%). Only dyspnea improvement was significant compared to placebo even at the 300 microg indacaterol dose. Compared to placebo, a 12-week treatment of the long-acting beta-agonist, indacaterol might not have a significant effect on cough or phlegm in stable COPD.

Analysis of the sputum and inflammatory alterations of the airways in patients with common variable immunodeficiency and bronchiectasis

INTRODUCTION: Common variable immunodeficiency is characterized by defective antibody production and recurrent pulmonary infections. Intravenous immunoglobulin is the treatment of choice, but the effects of Intravenous immunoglobulin on pulmonary defense mechanisms are poorly understood. OBJECTIVE: The aim of this study was to verify the impact of intravenous immunoglobulin on the physical properties of the sputum and on inflammatory alterations in the airways of patients with Common variable immunodeficiency associated with bronchiectasis. METHOD: The present study analyzed sputum physical properties, exhaled NO, inflammatory cells in the sputum, and IG titers in 7 patients with Common variable immunodeficiency and bronchiectasis with secretion, immediately before and 15 days after Intravenous immunoglobulin. A group of 6 patients with Common variable immunodeficiency and bronchiectasis but no sputum was also studied for comparison of the basal IgG level and blood count. The 13 patients were young (age=36±17 years) and comprised predominantly of females (n=11). RESULTS: Patients with secretion presented significantly decreased IgG and IgM levels. Intravenous immunoglobulin was associated with a significant decrease in exhaled NO (54.7 vs. 40.1 ppb, p<0.05), sputum inflammatory cell counts (28.7 vs. 14.6 cells/mm³, p<0.05), and a significant increase in respiratory mucus transportability by cough (42.5 vs. 65.0 mm, p < 0.05). CONCLUSION: We concluded that immunoglobulin administration in Common variable immunodeficiency patients results in significant improvement in indexes of inflammation of the airways with improvement in the transportability of the respiratory mucus by cough.

A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation.

Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.

Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis.

Sputum conversion is an important milestone in the management of pulmonary tuberculosis. Early sputum conversion is desirable. A controlled study was done to improve sputum conversion rate of current short course chemotherapy using immunomodulator containing mycobacterium w. The immunomodulator is very potent and freely available. It shares antigens with Mycobacterium tuberculosis. In a randomised pattern 69 of 134 patients suffering from pulmonary tuberculosis received the immunomodulator intradermally every 15 days along with chemotherapy. The use of the immunomodulator results in preponement of sputum conversion. The sputum conversion rate obtained by chemotherapy at 60 days was achieved latest by 30 days when mycobacterium w containing immunomodulator was used as an adjuvant therapy. This was found irrespective of bacterial load (1 +, minimal or 3+, maximal) in sputum or category (fresh or retreatment) of disease. The therapy was well tolerated.

Eficacia y seguridad de la cefodizima en el tratamiento de pacientes con infección de vías respiratorias bajas adquirirdas en la comunidad / Efficiency and safeness of cefodizime in the treatment of patients with community acquired of low respiratory tract

Se presentan los resultados de un estudio clínico abierto, no controlados, binacional, conducido en 73 pacientes hospitalizados con infecciones de vías respiratorias bajas adquiridas en la comunidad, tratados con 1 g de cefodizima una vez al días (OAD) administrada parenteralmente por inyección intramuscular, intravenosa o por infusión endovenosa. El objetivo fue evaluar la eficacia y seguridad del medicamento. La curación clínica, se evaluó por la desparición y/o mejoría de los síntomas relacionados a la infección (esputo purulento, tos, disnea y dolor torácico) y la resolución de la fiebre (ó 38ºC). La tasa de éxito se obtuvo en el 92.3 por ciento de los pacientes. La erradicación bacteriológica fue del 98 por ciento. Los microorganismos patógenos aislados con mayor frecuencia fueron: S. pneumoniae (53 por ciento), S aureus (20 por ciento) y K. pneumoniae (10 por ciento). En tres pacientes, los eventos adversos clínicos fueron considerados posiblemente relacionados con la medicación en estudio. Los resultados clínicos muestran que 1 g de cefodizima adminstrada una vez al día es un tratamiento eficaz y seguro en el tratamiento de pacientes adultos hospitalizados con neumonía adquirida en la comunidad

Factores de riesgo para resistencia a drogas antifímicas en Chiapas, México / Risk factors for drug-resistant tuberculosis in Chiapas, Mexico

Objetivo. Determinar los factores de riesgo para resistencia antifímica en pacientes con tuberculosis pulmonar, en cuatro jurisdicciones sanitarias del estado de Chispas, México. Material y métodos. Se realizó un estudio de casos y controles en el cual se incluyeron pacientes con tuberculosis pulmonar diagnosticados por medio de baciloscopía, notificados durante 1992. Se aplicó una encuesta que incluía variables relacionadas con el diagnóstico, tratamiento y seguimiento de los pacientes con tuberculosis pulmonar y se recolectaron muestras de expectoración para su análisis. La pruebas de sensibilidad se realizaron con el método de las proporciones. Se consideró a un paciente con infección de M. tuberculosis resistente cuando existían colonias desarrolladas en la presencia de una o más drogas antifímicas. El grupo control estuvo constituido por pacientes con resultados negativos a baciloscopías y cultivos, y en caso de ser positivo este último, con informe de M. tuberculosis sensible a las drogas estudiadas. Resultados. Del total de 18 individuos con cultivos positivos y desarrollo de M. tuberculosis, 13 (72 por ciento) fueron resistentes a una o más drogas antifímicas y 10 a dos o más drogas, de los cuales tres fueron resistentes a cinco antifímicos. La resitencia más alta fue para la isoniacida con 77 por ciento. Los factores de riesgo detectados en la población estudiada fueron la monoterapia (RM=34.2), los abandonos del tratamiento (RM=6.86), el tiempo prolongado de evolución de la enfermedad (RM=6.40) y los multitratamientos (RM=28.3). Conclusiones. La proporción tan alta de pacientes resistentes a drogas antifímicas (72 por ciento), denota un grave problema de salud pública y es de clara consecuencia de los problemas originados por el manejo inadecuado del tratamiento antituberculoso

Objectives. To determine risk factors for antibiotic resistance in patients with pulmonary tuberculosis in four Health Jurisdictions of the state of Chiapas. Material and Methods. A case-control study was carried out in patients diagnosed by acid fast smear during 1992. A questionnaire was applied which included variables related to the diagnosis, treatment and follow-up of the patients. Sputum samples were collected for culture and sensitivity tests. A case of drug-resistant pulmonary tuberculosis was defined as the presence of culture colonies showing resistance to one or more drugs. The control group was patients with negative smears and cultures or positive cultures for M. tuberculosis sensitive to the specific drugs. Results. Of the total of 18 individuals reported to have positive cultures, 13 (72.2%) were resistant to one or more drugs. Resistance to two or more drugs was found in 10 of them of which three were resistant to five antituberculosis drugs. The most frequent resistance was to isoniazid (77%). Risk factors for resistance encountered in this patient population were monotherapy (OR= 34.2), abandonment of treatment (OR= 6.86), a prolonged period of illness (OR= 6.40), delay in diagnosis and a history of prior therapy (OR= 28.3). Conclusions. The high proportion of patients resistant to antituberculosis therapy poses a public health problem and is a clear consequence of the problems arising from inadequate treatment.

Sputum production during recovery from acute asthma--effect of adrenal corticosteroids.

The effect of corticosteroid drugs on sputum production was studied in 74 patients of asthma. They were alternatively allotted to two different treatment schedules-conventional bronchodilator drugs alone and bronchodilators plus corticosteroids. All the subjects recovered, bringing out sputum in the process. However, the steroid treated group produced significantly less sputum than the other group. It is concluded that (a) sputum expectoration is a regular accompaniment of recovery from acute asthma and (b) steroids inhibit sputum production in acute asthma.

Estudos da estabilidade da secreçäo mucóide / Stability studies of mucus secretion

O objetivo do trabalho, é a determinaçäo de parâmetros definitórios do modelo de comportamento reológico da secreçäo mucóide das expectoraçöes, analisando as variaçöes produzidas em doentes tratadas ou näo como fármacos mucolíticos. Finalmente, é estudada a estabilidade da secreçäo mucóide frente a uma açäo de fricçäo repetitiva, definido o parâmetro de caracterizaçäo (coeficiente de perda logarítmica de viscosidade por ciclo), verificando, desta forma, sua estabilidade