关键词: 磺胺甲噁唑, 甲氧苄啶, 抗结核药, 微生物敏感性试验, 药物相互作用

Abstract: Objective  To evaluate the anti-mycobacterial efficacy of sulfamethoxazole（SMX）and trimethoprim（TMP） on Mycobacterium tuberculosis and analyze the interaction between SMX and other anti-TB drugs in vitro.  Methods The minimum inhibition concentrations (MICs) of TMP/SMX in 121 Mycobacterium tuberculosis (Mtb) strains were tested by microplate alamar blue assay(MABA). Eighteen clinical isolates were chosen by the stratified cluster sample method, and determined the interactions between SMX and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin, rifabutin in vitro by fractional inhibitory concentration index (FICI) method. Meanwhile, Mtb H37Rv strain was used as reference. The data were analyzed using SPSS software-version 13.0, nonparametric rank sum text was adopted for comparing the MIC of 3 groups, statistically significant difference was P<0.05.  Results  90.08% (109/121) isolates of Mtb could be inhibited by 1/19 μg/ml TMP/SMX. The MIC of TMP/SMX(1∶19) in 5 isolates was 2/38 μg/ml, 7 strains including 5 drug-sensitive strains and 2 MDR strains with MIC≥2/38 μg/ml. The MICs of TMP/SMX(1∶19) had no statistical significance among drug-sensitive strains, MDR strains and other drug-resistant strains (χ²=0.111，P=0.946). Drug combination testing did not display synergy between SMX and 7 other anti-TB drugs on H37Rv strain, except for with rifabutin（FICI 0.281）. Among 18 clinical isolates, 14（14/18，77.78%） exhibited synergy between SMX and rifabutin, in which FICI ranged from 0.205 to 1.063.  Conclusion TMP/SMX showed great anti-mycobacterical efficacy on Mtb clinical isolates in vitro, regardless of drug-resistant patterns. There were no synergy between SMX and 7 other anti-TB drugs in vitro, except for rifabutin.

Key words: Sulfamethoxazole, Trimethoprim, Antitubercular agents, Microbial sensitivity tests, Drug interactions