中国医药导报
中國醫藥導報
중국의약도보
China Medical Herald
2015年
31期
48-52,60
,共6页
鲍曼不动杆菌%防耐药突变浓度%突变浓度选择窗%舒巴坦%外膜蛋白
鮑曼不動桿菌%防耐藥突變濃度%突變濃度選擇窗%舒巴坦%外膜蛋白
포만불동간균%방내약돌변농도%돌변농도선택창%서파탄%외막단백
Acinetobacter baumannii%Mutant prevention concentration%Mutant selection window%Sulbactam%Outer membrane
目的：探索鲍曼不动杆菌耐药机制，完善防耐药突变浓度(MPC)理论，指导临床合理用药。方法通过测定临床分离鲍曼不动杆菌的MPC相关参数，研究舒巴坦的防耐药突变能力，并对突变浓度诱导菌株进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)，探索外膜蛋白(OMP)表达量与耐药之间关系。结果舒巴坦对临床分离5株鲍曼不动杆菌耐药选择指数分别为6.4、7.2、5.6、9.9、5.6，诱导后的菌株OMP 29 kD条带减弱，提示鲍曼不动杆菌在突变浓度的舒巴坦诱导下，碳青霉烯耐药相关性外膜蛋白(CarO)低表达。结论舒巴坦对鲍曼不动杆菌耐药突变选择窗(MSW)的形成与CarO低表达可能密切相关，OMP的缺失可能是鲍曼不动杆菌耐药的首要机制；舒巴坦药代动力学参数表明，在临床应用中应避免其单独使用，联合用药可以减小或者关闭MSW，并减慢耐药菌株的产生速度。
目的：探索鮑曼不動桿菌耐藥機製，完善防耐藥突變濃度(MPC)理論，指導臨床閤理用藥。方法通過測定臨床分離鮑曼不動桿菌的MPC相關參數，研究舒巴坦的防耐藥突變能力，併對突變濃度誘導菌株進行十二烷基硫痠鈉-聚丙烯酰胺凝膠電泳(SDS-PAGE)，探索外膜蛋白(OMP)錶達量與耐藥之間關繫。結果舒巴坦對臨床分離5株鮑曼不動桿菌耐藥選擇指數分彆為6.4、7.2、5.6、9.9、5.6，誘導後的菌株OMP 29 kD條帶減弱，提示鮑曼不動桿菌在突變濃度的舒巴坦誘導下，碳青黴烯耐藥相關性外膜蛋白(CarO)低錶達。結論舒巴坦對鮑曼不動桿菌耐藥突變選擇窗(MSW)的形成與CarO低錶達可能密切相關，OMP的缺失可能是鮑曼不動桿菌耐藥的首要機製；舒巴坦藥代動力學參數錶明，在臨床應用中應避免其單獨使用，聯閤用藥可以減小或者關閉MSW，併減慢耐藥菌株的產生速度。
목적：탐색포만불동간균내약궤제，완선방내약돌변농도(MPC)이론，지도림상합리용약。방법통과측정림상분리포만불동간균적MPC상관삼수，연구서파탄적방내약돌변능력，병대돌변농도유도균주진행십이완기류산납-취병희선알응효전영(SDS-PAGE)，탐색외막단백(OMP)표체량여내약지간관계。결과서파탄대림상분리5주포만불동간균내약선택지수분별위6.4、7.2、5.6、9.9、5.6，유도후적균주OMP 29 kD조대감약，제시포만불동간균재돌변농도적서파탄유도하，탄청매희내약상관성외막단백(CarO)저표체。결론서파탄대포만불동간균내약돌변선택창(MSW)적형성여CarO저표체가능밀절상관，OMP적결실가능시포만불동간균내약적수요궤제；서파탄약대동역학삼수표명，재림상응용중응피면기단독사용，연합용약가이감소혹자관폐MSW，병감만내약균주적산생속도。
Objective To explore Acinetobacter baumannii resistance mechanisms and improve mutant prevention con-centration (MPC) theory for guiding clinical therapy. Methods The mutant prevention ability of Sulbactam was investi-gated by measuring relevant parameter of MPC of the clinically isolated Acinetobacter baumannii. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to explore the relationship between outer membrane protein expression of mutant concentration induced strain and drug resistance. Results The resistance selection index of Sulbactam against five clinically isolated Acinetobacter baumannii was 6.4, 7.2, 5.6, 9.9 and 5.6 respectively. The membrane protein band at 29 kD was weaken after the mutant induction, which indicated that the expression of Carbapenem associated resis-tance outer membrane protein (CarO) of Acinetobacter baumannii induced by Sulbactam at mutation concentration was low. Conclusion The mutant selection window (MSW) formation of Acinetobacter baumannii caused by Sulbactam may be closely related to low expression of CarO. The primary mechanism of drug resistance in Acinetobacter baumannii maybe owing to its membrane protein deficiency. The pharmacokinetic parameters of Sulbactam indicate that single medication should be avoided in clinical application. Combination drug therapy can reduce or close MSW and slow down the speed of drug-resistant strains generation in treatment of Acinetobacter baumannii infection.
