Abstract: Objective  To study the phenotypically resistant characteristics and therapeutic effect of antitubercular drugs on M. tuberculosis clinical isolates from the patients with tuberculous meningitis (TBM).  Methods Five hundred cerebrospinal fluid (CSF) from suspected patients with tuberculous miningitis were cultured with Bactec MGIT 960. Twenty-five strains were isotated, and then identified the species by 16S rRNA gene sequencing, detected 14 anti-tuberculous drug susceptibility by Bactec MGIT 960 and 12 anti-tuberculous drug susceptibility by the proportional method of conventional solid culture. The minimal inhibitory concentrations (MICs) of 16 anti-tuberculous drugs on these isolates were determined. The bacterial sterilization rate was determined by calculating the ratio of maximal plasma concentration (C_max)/MIC to evaluated thetherapeutic effect of drugs on M. tuberculosis. Results Of 25 M. tuberculosis isolates, 13 were resistant to any anti-tuberculous drugs, 3 were multidrug-resistant. The ratios of C_max/MIC for rifampicin, moxifloxacin, levofloxacin, clofazimine, and p-aminosalicylic acid were 19.880, 63.333, 19.149, 75.000, and 50.855, respectively.  Conclusion  Most drug-resistant isolates from TBM patients were phenotypically resistant to isoniazid or rifampicin, the least isolates were phenotypically resistant to quinolone. The C_max/MIC values of moxifloxacin, clofazimine, p-aminosalicylic acid, levofloxacin and rifampicin were higher, suggesting that the combination of high doses of rifampicin and fluoroquinolones might improve the therapeutic effect of TBM. P-aminosalicylic acid and clofazimine might play an better role in antituberculous treatment of TBM.

Key words: Tuberculosis, meningeal/drug therapy, Phenotype, Microbial sensitivity tests, Treatment outcome