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

• Published in: The Journal of infectious diseases Vol. 192; no. 1; pp. 79 - 88
• Main Authors: Thwaites, Guy E., Lan, Nguyen Thi Ngoc, Dung, Nguyen Huy, Quy, Hoang Thi, Oanh, Do Thi Tuong, Thoa, Nguyen Thi Cam, Hien, Nguyen Quang, Thuc, Nguyen Tri, Hai, Nguyen Ngoc, Bang, Nguyen Duc, Lan, Nguyen Ngoc, Duc, Nguyen Hong, Tuan, Vu Ngoc, Hiep, Cao Huu, Chau, Tran Thi Hong, Mai, Pham Phuong, Dung, Nguyen Thi, Stepniewska, Kasia, White, Nicholas J., Hien, Tran Tinh, Farrar, Jeremy J.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01.07.2005; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Antitubercular Agents - therapeutic use; Antituberculars; Bacteria; Cerebrospinal fluid; Drug resistance; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fever; Health outcomes; Human immunodeficiency virus; Humans; Infectious diseases; Male; Meningeal tuberculosis; Middle Aged; Mycobacterium tuberculosis; Prospective Studies; Pulmonary tuberculosis; Treatment Outcome; Tropical medicine; Tuberculosis, Meningeal - drug therapy; Tuberculosis, Meningeal - microbiology; Tuberculosis, Meningeal - mortality
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/430616

BackgroundTuberculous 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 MethodsWe 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 ResultsOf 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 ConclusionsIsoniazid 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