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

被引：59

作者：

Brindle R. ^{[1
]}

Odhiambo J. ^{[2
]}

Mitchison D. ^{[3
]}

机构：

[1] Public Health Laboratory, Portsmouth Hospital, Portsmouth PO3 6AO, Milton Rd.

[2] Kenya Medical Research Institute, Nairobi

[3] Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 0RE, Cranmer Terrace

来源：

BMC Pulmonary Medicine | / 1卷 / 1期

关键词：

Rifampicin; Isoniazid; Pulmonary Tuberculosis; Pyrazinamide; Kill Rate;

D O I：

10.1186/1471-2466-1-2

中图分类号：

学科分类号：

摘要：

Background: Since 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. Methods: A 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). Results: During 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. Conclusions: Surrogate 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. © 2001 Brindle et al; licensee BioMed Central Ltd.

引用

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