Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis.
Caws M., Thwaites GE., Duy PM., Tho DQ., Lan NTN., Hoa DV., Chau TTH., Huyen MNT., Anh PTH., Chau NVV., Chinh TNT., Stepniewska K., Farrar J.
SettingTertiary referral hospitals in southern Vietnam.ObjectiveMolecular characterisation of multidrug-resistant (MDR) tuberculous meningitis (TBM).DesignMycobacterium 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.ResultsWhile 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.ConclusionRMP 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.