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目的探讨莫西沙星(MXF)与左氧氟沙星(LVF)对结核分枝杆菌的交叉耐药性及耐药基因突变位点,为临床用药提供理论依据。方法选取结核分枝杆菌标准株H37Rv和73株左氧氟沙星耐药的耐多药结核分枝杆菌(MDR-TB)临床分离株以及5株对左氟沙星敏感的MDR-TB临床分离株,以试管二倍稀释法采用7H9培养基,测定以上菌株对MXF和LVF的MIC;通过直接测序法测定gyrA基因喹诺酮类药物耐药决定区(QRDR)320 bp的基因突变位点。结果MXF的MIC比LVF低4～8倍;H37Rv未发生gyrA基因突变;78株MDR-TB临床分离株均有Ser95Thr突变;73株LVF耐药的MDR-TB菌株中,35株(47.94%)对LVF低耐药(MIC为1～8μg/ml)的菌株和31株(42.46%)对LVF高耐药株中,除4株只有Ser95Thr突变外,其他菌株同时有Ala90Val、Asp94His、Asp94Asn、Asp94Gly、Asp94Ala、Asp94Tyr突变。结论莫西沙星较左氧氟沙星的抗结核活性强4～8倍,为不完全交叉耐药;gyrA基因90位和94位突变与MDR-TB菌株对LVF、MXF耐药有关,低耐药与高耐药的突变氨基酸种类有差别,有望将测序作为临床左氟沙星分子药敏试验方法。
Objective To investigate the cross-resistance of drug-resistant Mycobacterium tuberculosis to moxifloxacin (MXF) and levofloxacin (LVF) and to provide a theoretical basis for clinical drug use. Methods The clinical isolates of Mycobacterium tuberculosis H37Rv and 73 levofloxacin-resistant multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains and 5 clinical isolates of lefloxacin-sensitive MDR-TB were selected. The MIC of MICF and LVF was determined by 7H9 medium in double dilution method. The 320 bp gene mutation of quinolone resistance-determining region (QRDR) of gyrA gene was determined by direct sequencing. Results The MIC of MXF was 4 to 8 times lower than that of LVF. No gyrA gene mutation occurred in H37Rv. Ser95Thr mutation was found in 78 MDR-TB clinical isolates. Of the 73 LVF resistant MDR-TB strains, 35 (47.94% Among the strains with low resistance to LVF (MIC 1 ~ 8μg / ml) and 31 strains (42.46%) with high resistance to LVF, except for the Ser95Thr mutation in only 4 strains, there were Ala90Val, Asp94His, Asp94Asn, Asp94Gly , Asp94Ala, Asp94Tyr mutation. CONCLUSION Moxifloxacin is 4 to 8 times stronger than levofloxacin in anti-TB activity and is incompletely cross-resistant. The 90 and 94 mutations of gyrA gene are associated with MDR-TB strains resistant to LVF and MXF, low resistance and high resistance There are differences in the types of amino acid mutation drugs, is expected to be sequenced as a clinical levofloxacin molecular susceptibility testing methods.