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Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

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Heemskerk, A Dorothee, Bang, Nguyen D, Mai, Nguyen T H, Chau, Tran T H, Phu, Nguyen H, Loc, Pham P, Chau, Nguyen V V, Hien, Tran T, Dung, Nguyen H, Lan, Nguyen T N, Lan, Nguyen H, Lan, Nguyen N, Phong, Le T, Vien, Nguyen N, Hien, Nguyen Q, Yen, Nguyen T B, Ha, Dang T M, Day, Jeremy N, Caws, Maxine ORCID: https://orcid.org/0000-0002-9109-350X, Merson, Laura, Thinh, Tran T V, Wolbers, Marcel, Thwaites, Guy E and Farrar, Jeremy J (2016) 'Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis'. New England Journal of Medicine, Vol 374, Issue 2, pp. 124-134.

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Abstract

BACKGROUND
Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.

METHODS
We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.

RESULTS
A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).

CONCLUSIONS
Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).

Item Type: Article
Subjects: WC Communicable Diseases > Infection. Bacterial Infections > Other Bacterial Infections. Zoonotic Bacterial Infections > WC 302 Actinomycetales infections. Mycobacterium infections
WF Respiratory System > Tuberculosis > WF 360 Drug therapy
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1056/NEJMoa1507062
Depositing User: Julie Franco
Date Deposited: 04 Aug 2016 13:51
Last Modified: 06 Dec 2018 11:23
URI: http://archive.lstmed.ac.uk/id/eprint/6033

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