大环内酯类抗菌药物对加替沙星透过细菌生物被膜的影响

Effects of Macrolides on Permeability of Gatifloxacin Across Bacterial Biofilm

目的研究克拉霉素(CLR)和阿奇霉素(AZT)对加替沙星(GAT)透过铜绿假单胞菌生物被膜的影响。方法使用0.22μm孔径医用微孔滤膜建立了铜绿假单胞菌生物被膜体外模型;采用改良的Franz扩散池,用HPLC方法测定GAT透过细菌生物被膜的情况,并测定64μg/mlCLR和AZT对GAT透过被膜的影响。结果经过7d的连续培养后,铜绿假单胞菌可在微孔滤膜表面形成均匀、致密的被膜,被膜中多糖蛋白复合物的含量为(57.69±32.97)μg/cm2,被膜中活菌数为(2.15×107)CFU/cm2;经测定,GAT可缓慢地通过细菌生物被膜,约7h后达到平衡,而合用64μg/ml的CLR或AZT可明显增加第3～6小时期间GAT的透过速度。结论以医用微孔滤膜为载体可成功地建立铜绿假单胞菌生物被膜体外模型;大环内酯类药物,如CAM或AZT可以显著地促进GAT对细菌生物被膜的透过。

OBJECTIVE To investigate the effects of clarithromycin and azithromycin on the permeability of (gatifloxacin) (GAT) across the bacterial biofilm of Pseudomonas aeruginosa. METHODS In vitro model of (P. aeruginosa) biofilm was established using 0.22 μm dimension medical micropore film. The permeability of GAT across bacterial biofilm was observed in modified Franz diffusion cell and the effects of 64 μg/ml clarithromycin and azithromycin on it were measured by HPLC. RESULTS After seven days′ continuous cultivation, P. aeruginosa could establish well-distributed and compact biofilm in the surface of micropore film, in which the content of glycocalyx was (57.69±32.97)μg/cm^2 and the amount of viable organism was ((2.15×10~7)) CFU/cm^2; (gatifloxacin) could slowly penetrate bacterial biofilm and the equilibration was achieved in 7h. When combined with 64 μg/ml clarithromycin or azithromycin, the permeation rate of gatifloxacin on h3 to h6 significantly (increased.) CONCLUSIONS In vitro model of P. aeruginosa biofilm can be successfully established using medical micropore film as a supporter; macrolide drugs such as clarithromycin and azithromycin can significantly promote the permeability of GAT across bacterial biofilm.