title: Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis.
abstract: 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.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. guy.thwaites@btinternet.com
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.forename: Nguyen Thi Ngoc
authors.initials: NT
authors.lastname: Lan
authors.forename: Nguyen Huy
authors.initials: NH
authors.lastname: Dung
authors.forename: Hoang Thi
authors.initials: HT
authors.lastname: Quy
authors.forename: Do Thi Tuong
authors.initials: DT
authors.lastname: Oanh
authors.forename: Nguyen Thi Cam
authors.initials: NT
authors.lastname: Thoa
authors.forename: Nguyen Quang
authors.initials: NQ
authors.lastname: Hien
authors.forename: Nguyen Tri
authors.initials: NT
authors.lastname: Thuc
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Hai
authors.forename: Nguyen Duc
authors.initials: ND
authors.lastname: Bang
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Lan
authors.forename: Nguyen Hong
authors.initials: NH
authors.lastname: Duc
authors.forename: Vu Ngoc
authors.initials: VN
authors.lastname: Tuan
authors.forename: Cao Huu
authors.initials: CH
authors.lastname: Hiep
authors.forename: Tran Thi Hong
authors.initials: TT
authors.lastname: Chau
authors.forename: Pham Phuong
authors.initials: PP
authors.lastname: Mai
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Dung
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality
chemical_list: D000995:Antitubercular Agents