枸橼酸铋钾对幽门螺杆菌耐药菌株体外抗菌活性研究

目的铋制剂被广泛应用于幽门螺杆菌（H．pylori）感染的根除治疗，目的在于了解枸橼酸铋钾在体外对H．pylori耐药菌株是否存在抗菌活性及枸橼酸铋钾在体外对甲硝唑和克拉霉素抗H．pylori耐药菌株活性的影响。方法选取H．pylori标准菌株NCTC11637（对照）和8株l临床分离H．pylori耐药菌株作为实验菌株：抑菌研究采用琼脂稀释法测定枸橼酸铋钾对H．pylori菌株的最小抑菌浓度（MIC），通过E试验法在含枸橼酸铋钾培养基和普通培养基上分别测定甲硝唑或克托霉素对H．pylori菌株的MIC值。杀菌研究采用时间一杀菌曲线法，分别在含有枸橼酸铋钾、甲硝唑、克拉霉素及枸橼酸铋钾与甲硝唑或克拉霉素混合物的液体培养基中对H．pylori标准菌株NCTC11637及l临床分离的H．pylori耐药菌株进行培养，分别计算空白对照组和各实验组0、4、8、24h的细菌数量，采用半对数法绘制时间-杀菌曲线：结果枸橼酸铋钾对H．pylori标准菌株及临床分离的H．pylori耐药菌株平均MIC值为2．6mg／L（铋）：枸橼酸铋钾降低甲硝哗和克拉霉素对H．pylori耐药菌株的MIC值。枸橼酸铋钾1mg／L（铋）对标准菌株H．pylori11637具有明显的体外杀菌作用，4mg／L（铋）对临床分离耐药菌株也具有明显的体外杀菌作用，其杀菌效果随剂量增加而增强：、枸橼酸铋钾与抗生素混合物对H．pylori标准菌株及临床耐药菌株的体外杀菌作用增强。结论枸橼酸铋钾对H．pylori标准菌株及临床分离的H．pylori耐药菌株均有体外抑菌和杀菌作用，并且与甲硝唑或克拉霉素联用对标准菌株及临床分离的H．pylori耐药菌株具有体外协同抑菌或杀菌作用。

Vitro activity of bismuth potassium citrate agaiust clinical isolates of antibiotic-resistant Helicobacter pylori

Objective Bismuth-containing drugs are widely used in the treatment of Helicobacter pylori （H. pylori） associated diseases. It has been reported that bismuth has an antimicrobial activity in itself. With the growing emergence of H. pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds on antibiotic-resistant isolates is required. The aim of this study was to evaluate the activity of bismuth potassium citrate against clinical isolates of antibiotic-resistant H. pylori. Methods In this in vitro study, bismuth potassium citrate and bismuth potassium citrate combining with metronidazol or clarithromycin were investigated for bacteriostatic activity using agar dilution or E-test methodology, and for bactericidal activity using time-kill methology. Eight strains of antibiotic-resistant clinical isolates of H. pylori and H. pylori NCTC11637 were examined. Results Bismuth potassium citrate was ac- tive against antibiotic-resistant H. pylorl mean inhibitory concentration, 2.6 mg/mL （Bi）], while it was synergistic with antibiotics. Bismuth potassium citrate showed bactericidal activity to H. pylori NCTC11637 1 mg/mL（Bi） ], but against the resistant strain the agent showed less killing 4 mg/mL （Bi） ]. The strength of bactericidal activity was related to the concentration of Bi agent. The combination of bismuth potassium citrate and metronidazole or clarithromycin, to an antibiotic-resistant strain of H. pylori showed increasing bactericidal activity. Conclusion Bismuth potassium citrate have inhibitory and cidal activity to antibiotic-resistant H. pylori strains in vitro, and it is synergistic with antibiotics.