Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosisReportar como inadecuado




Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Pulmonary Medicine

, 1:2

First Online: 21 November 2001Received: 09 October 2001Accepted: 21 November 2001

Abstract

BackgroundSince the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required.

MethodsA suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone SHT or rifampicin + pyrazinamide SHRZ.

ResultsDuring days 0–2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2–7 p = 0.044, due to rifampicin, and during days 14–28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2–28 p = 0.0005 in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2–28 p = 0.007, mainly during days 2–7.

ConclusionsSurrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2466-1-2 contains supplementary material, which is available to authorized users.

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Autor: Richard Brindle - Joseph Odhiambo - Denis Mitchison

Fuente: https://link.springer.com/



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