细胞膜渗透性对氟喹诺酮耐药表皮葡萄球菌药物敏感性的影响

Correlation between susceptibility of fluoroquinolone-resistant Staphylococcus epidermidis and declined membrane permeability

目的 研究表皮葡萄球菌细胞膜渗透性下降对氟喹诺酮 (FQNs)类药物敏感性的影响。方法 比较合用杆菌肽 (BAC)、EDTA前后 ,敏感菌及耐药菌分别对环丙沙星 (CPLX)、司帕沙星 (SPLX)药物敏感性的变化 ;测定敏感菌、耐药菌细胞内的药物浓度及乙二胺四乙酸 (EDTA)对药物浓度的影响。结果 杆菌肽与 2种FQNs合用对 8株突变耐药菌的部分浓度抑菌指数分别为 0 .5 9和 0 .72 ,表现出协同或相加的抗菌作用。合用EDTA对敏感菌株的MIC影响不大 ,但可显著增加耐药菌对FQNs的敏感性 ,合用 2 .0mmol·L-1EDTA后CPLX和SPLX对耐药菌的MIC均下降了 90 %以上。敏感菌细胞内的FQNs药物浓度明显高于耐药菌 ,合用 2mmol·L-1EDTA可使耐药菌细胞内的CPLX浓度从 40ng·10 -9(cells)增加到 30 0ng·10 -9(cells) ,SPLX的浓度从 12 0ng·10 -9(cells)增加到 30 0ng·10 -9(cells) ,而敏感菌细胞内的药物浓度上升不超过 2 0 %。结论 FQNs耐药的表皮葡萄球菌细胞膜的渗透性显著下降 ,导致进入细胞内的药物减少而引起细菌耐药。合用BAC ,EDTA等可提高细胞膜渗透性的药物或试剂后 。

OBJECTIVE: To investigate the correlation between the susceptibility of fluoroquinolone-resistant Staphylococcus epidermidis to antibiotics and the decreased cell membrane permeability. METHODS: To evaluate the influence of the decreased cell membrane permeability on resistant mutants, bacteria's FQNs susceptibility treated with bacitracin and EDTA was determined. The intracellular drug concentrations of ciprofloxacin (CPLX) and sparfloxacin (SPLX) were also quantified in order to analyze the strength of permeability barrier. RESULTS: When two kinds of FQNs combined with bacitracin, the FIC index of resistant mutants were 0.59 (CPLX) and 0.72 (SPLX), respectively. All the mutants responded synergism or addition effect, no autonomy and antagonism combination was observed. The MICs of sensitive strains gained an limited alteration to CPLX and SPLX combined with EDTA, while the resistant mutants's MIC decreased markedly. 2 mmol&middotL-1 EDTA decreased mutants's MIC for over 90% to CPLX and SPLX. The intracellular drug concentration of CPLX in resistant mutants rose from 40 ng&middot 10-9(cells) to 300 ng&middot10-9 (cells) combined with 2 mmol&middotL-1 EDTA; The SPLX's concentration rose from 120 ng&middot10-9 (cells) to 300 ng&middot 10-9 (cells). On the other hand, the intracellular drug concentration in sensitive bacteria increased less than 20%. CONCLUSION: The decreased cell membrane permeability resulted in Staphyloxoccus epidermidis's FQNs-resistance. The resistant mutants's FQNs-susceptibility may be improved. While the cell membrane permeability may be increased.