Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis.
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.
Caws
M
M
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. mcaws@hotmail.com
Thwaites
G E
GE
Duy
P M
PM
Tho
D Q
DQ
Lan
N T Ngoc
NT
Hoa
D V
DV
Chau
T T Hong
TT
Huyen
M N Thu
MN
Anh
P T Hoang
PT
Chau
N V V
NV
Chinh
T N T
TN
Stepniewska
K
K
Farrar
J
J
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
D000995:Antitubercular Agents; D004269:DNA, Bacterial; D015335:Molecular Probes; D007538:Isoniazid