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1 July 2005

Volume 192, Number 1
The Journal of Infectious Diseases 2005;192:79–88
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19201-0013$15.00
DOI: 10.1086/430616
MAJOR ARTICLE

Effect of Antituberculosis Drug Resistance on Response to Treatment and Outcome in Adults with Tuberculous Meningitis

Guy E. Thwaites,1,4,a

Nguyen Thi Ngoc Lan,2

Nguyen Huy Dung,2

Hoang Thi Quy,2

Do Thi Tuong Oanh,2

Nguyen Thi Cam Thoa,2

Nguyen Quang Hien,2

Nguyen Tri Thuc,2

Nguyen Ngoc Hai,2

Nguyen Duc Bang,2

Nguyen Ngoc Lan,2

Nguyen Hong Duc,2

Vu Ngoc Tuan,2

Cao Huu Hiep,2

Tran Thi Hong Chau,3

Pham Phuong Mai,3

Nguyen Thi Dung,3

Kasia Stepniewska,4

Nicholas J. White,1,4

Tran Tinh Hien,3 and

Jeremy J. Farrar1,4

1Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 2Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, and 3Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; 4Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom

Background.Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain.

Methods.We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first‐line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9‐month morbidity and mortality were compared between adults infected with susceptible and those infected with drug‐resistant organisms.

Results.Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21–26.32]) and was independently associated with human immunodeficiency virus infection.

Conclusions.Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first‐line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.

Received 18 October 2004; accepted 29 December 2004; electronically published 20 May 2005.

  • (See the editorial commentary by Seaworth, on pages 10–2.)

Reprints or correspondence: Dr. Guy E. Thwaites, Dept. of Infectious Diseases and Microbiology, Brighton and Sussex University Hospital, Eastern Rd., Brighton, Sussex, BN2 5BE, United Kingdom ().

Cited by

Dominique J. Pepper, Suzaan Marais, Gary Maartens, Kevin Rebe, Chelsea Morroni, Molebogeng X. Rangaka, Tolu Oni, Robert J. Wilkinson, and Graeme Meintjes. (2009) Neurologic Manifestations of Paradoxical Tuberculosis‐Associated Immune Reconstitution Inflammatory Syndrome: A Case Series. Clinical Infectious Diseases 48:11, e96-e107
Online publication date: 1-Jun-2009.
Abstract-Full Text-PDF Version (289 kB)
B.-M. Mackert, J. Conradi, C. Loddenkemper, F.K.H. Landeghem, R. Loddenkemper, R. Ignatius, T. Schneider. (2008) Neurotuberkulose. Der Nervenarzt 79:2, 153-166
Online publication date: 1-Mar-2008.
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Thomas F. Byrd, Larry E. Davis. (2007) Multidrug-resistant tuberculous meningitis. Current Neurology and Neuroscience Reports 7:6, 470-475
Online publication date: 1-Dec-2007.
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Diego Cecchini, Juan Ambrosioni, Clarisa Brezzo, Marcelo Corti, Ana Rybko, Marcela Perez, Susana Poggi, Marta Ambroggi. (2007) Tuberculous meningitis in HIV-infected patients: drug susceptibility and clinical outcome. AIDS 21:3, 373???374
Online publication date: 1-Feb-2007.
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A.M. Bal. (2007) Isoniazid prophylaxis in end-stage renal disease. Transplant Infectious Disease 8:4, 242-243
Online publication date: 1-Jan-2007.
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Guy E. Thwaites, Nguyen Duc Bang, Nguyen Huy Dung, Hoang Thi Quy, Do Thi Tuong Oanh, Nguyen Thi Cam Thoa, Nguyen Quang Hien, Nguyen Tri Thuc, Nguyen Ngoc Hai, Nguyen Thi Ngoc Lan, Nguyen Ngoc Lan, Nguyen Hong Duc, Vu Ngoc Tuan, Cao Huu Hiep, Tran Thi Hong Chau, Pham Phuong Mai, Nguyen Thi Dung, Kasia Stepniewska, Cameron P. Simmons, Nicholas J. White, Tran Tinh Hien, and Jeremy J. Farrar. (2005) The Influence of HIV Infection on Clinical Presentation, Response to Treatment, and Outcome in Adults with Tuberculous Meningitis. The Journal of Infectious Diseases 192:12, 2134-2141
Online publication date: 15-Dec-2005.
Abstract-Full Text-PDF Version (197 kB)
Barbara J. Seaworth. (2005) It Is Too Early to Discount the Contribution of Isoniazid to the Treatment of Tuberculous Meningitis. The Journal of Infectious Diseases 192:1, 10-12
Online publication date: 1-Jul-2005.
Citation-Full Text-PDF Version (57 kB)

  • Financial support: Wellcome Trust of Great Britain.

  • Present affiliation: Department of Infectious Diseases and Microbiology, Brighton and Sussex University Hospital.

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