Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis.
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.
Thwaites
Guy E
GE
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. guy.thwaites@btinternet.com
Lan
Nguyen Thi Ngoc
NT
Dung
Nguyen Huy
NH
Quy
Hoang Thi
HT
Oanh
Do Thi Tuong
DT
Thoa
Nguyen Thi Cam
NT
Hien
Nguyen Quang
NQ
Thuc
Nguyen Tri
NT
Hai
Nguyen Ngoc
NN
Bang
Nguyen Duc
ND
Lan
Nguyen Ngoc
NN
Duc
Nguyen Hong
NH
Tuan
Vu Ngoc
VN
Hiep
Cao Huu
CH
Chau
Tran Thi Hong
TT
Mai
Pham Phuong
PP
Dung
Nguyen Thi
NT
Stepniewska
Kasia
K
White
Nicholas J
NJ
Hien
Tran Tinh
TT
Farrar
Jeremy J
JJ
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
D000995:Antitubercular Agents