title: Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis.
abstract: METHODS
  Tertiary referral hospitals in southern Vietnam.
  
  
  OBJECTIVE
  Molecular characterisation of multidrug-resistant (MDR) tuberculous meningitis (TBM).
  
  
  METHODS
  Mycobacterium tuberculosis isolates from the cerebrospinal fluid (CSF) of 198 Vietnamese adults were compared with 237 isolates from patients with pulmonary tuberculosis (PTB) matched for age, sex and residential district. Isolates resistant to isoniazid or rifampicin (RMP) were sequenced in the rpoB and katG genes, inhA promoter and oxyR-ahpC intergenic regions.
  
  
  RESULTS
  While drug resistance rates were lower in the CSF (2.5% MDR) than pulmonary isolates (5.9% MDR), the difference was not significant. The most commonly mutated codons were 531, 526 and 516 in rpoB and 315 in katG. Four novel triple mutants in rpoB were identified.
  
  
  CONCLUSIONS
  RMP resistance is a good surrogate marker for MDR-TBM in this setting. However, probes directed against these three codons would have a maximum sensitivity of only 65%. A rapid phenotypic detection test may be more applicable for the diagnosis of MDR-TBM.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. mcaws@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Caws
authors.forename: G E
authors.initials: GE
authors.lastname: Thwaites
authors.forename: P M
authors.initials: PM
authors.lastname: Duy
authors.forename: D Q
authors.initials: DQ
authors.lastname: Tho
authors.forename: N T Ngoc
authors.initials: NT
authors.lastname: Lan
authors.forename: D V
authors.initials: DV
authors.lastname: Hoa
authors.forename: T T Hong
authors.initials: TT
authors.lastname: Chau
authors.forename: M N Thu
authors.initials: MN
authors.lastname: Huyen
authors.forename: P T Hoang
authors.initials: PT
authors.lastname: Anh
authors.forename: N V V
authors.initials: NV
authors.lastname: Chau
authors.forename: T N T
authors.initials: TN
authors.lastname: Chinh
authors.forename: K
authors.initials: K
authors.lastname: Stepniewska
authors.forename: J
authors.initials: J
authors.lastname: Farrar
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D015335:Molecular Probes; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D013183:Sputum / Q000382:microbiology; D014390:Tuberculosis, Meningeal / Q000188:drug therapy* / Q000382:microbiology*; D014744:Vietnam
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D015335:Molecular Probes; D007538:Isoniazid