中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2014年
26期
2055-2058
,共4页
徐立升%刘明涛%张芸%亓倩%李玉
徐立升%劉明濤%張蕓%亓倩%李玉
서립승%류명도%장예%기천%리옥
假单胞菌,铜绿%突变%抗药性,细菌%外排泵抑制剂
假單胞菌,銅綠%突變%抗藥性,細菌%外排泵抑製劑
가단포균,동록%돌변%항약성,세균%외배빙억제제
Pseudomonas aeruginosa%Mutation%Drug resistance,bacterial%Efflux pump inhibitors
目的:探讨抗菌药联合外排泵抑制剂( EPI)对铜绿假单胞菌耐药突变选择窗的影响。方法选择铜绿假单胞菌标准株,测定美罗培南、头孢他啶、阿米卡星、环丙沙星4种药物单药最低抑菌浓度( MIC);棋盘格法测定联合利血平、奥美拉唑、阿奇霉素、羰基氰化物间氯苯腙( CCCP )、苯丙氨酸-精氨酸-β-萘胺(PAβN)5种EPI抗菌药物的MIC。琼脂平板二倍稀释法测定抗菌药物单药以及联合EPI的防耐药突变浓度(MPC),计算相应的选择指数(MPC/MIC);分别测定美罗培南、头孢他啶、环丙沙星联合阿米卡星,阿米卡星联合环丙沙星后的选择指数。在临床株中检测美罗培南、头孢他啶、阿米卡星、环丙沙星单药及与CCCP联合后的MIC、MPC及选择指数。结果在标准株,美罗培南、头孢他啶、阿米卡星、环丙沙星单药的选择指数分别为>32,>32,16,16;与利血平联合后选择指数分别为16、16、16、8;与奥美拉唑联合后分别为16、32、16、8;与阿奇霉素联合后分别为8、16、16、8;与CCCP联合后分别为8、8、16、8;与PAβN联合后分别为8、16、16、8。美罗培南、头孢他啶、环丙沙星分别与阿米卡星联合后的选择指数为4、4、8。阿米卡星与环丙沙星联合后阿米卡星的选择指数为4。在临床株,环丙沙星联合CCCP后选择指数较单药显著降低。结论除阿米卡星外,美罗培南、头孢他啶、环丙沙星联合EPI可明显降低MIC及MPC,环丙沙星联合CCCP可缩小突变选择窗,有利于减少耐药突变体的产生。
目的:探討抗菌藥聯閤外排泵抑製劑( EPI)對銅綠假單胞菌耐藥突變選擇窗的影響。方法選擇銅綠假單胞菌標準株,測定美囉培南、頭孢他啶、阿米卡星、環丙沙星4種藥物單藥最低抑菌濃度( MIC);棋盤格法測定聯閤利血平、奧美拉唑、阿奇黴素、羰基氰化物間氯苯腙( CCCP )、苯丙氨痠-精氨痠-β-萘胺(PAβN)5種EPI抗菌藥物的MIC。瓊脂平闆二倍稀釋法測定抗菌藥物單藥以及聯閤EPI的防耐藥突變濃度(MPC),計算相應的選擇指數(MPC/MIC);分彆測定美囉培南、頭孢他啶、環丙沙星聯閤阿米卡星,阿米卡星聯閤環丙沙星後的選擇指數。在臨床株中檢測美囉培南、頭孢他啶、阿米卡星、環丙沙星單藥及與CCCP聯閤後的MIC、MPC及選擇指數。結果在標準株,美囉培南、頭孢他啶、阿米卡星、環丙沙星單藥的選擇指數分彆為>32,>32,16,16;與利血平聯閤後選擇指數分彆為16、16、16、8;與奧美拉唑聯閤後分彆為16、32、16、8;與阿奇黴素聯閤後分彆為8、16、16、8;與CCCP聯閤後分彆為8、8、16、8;與PAβN聯閤後分彆為8、16、16、8。美囉培南、頭孢他啶、環丙沙星分彆與阿米卡星聯閤後的選擇指數為4、4、8。阿米卡星與環丙沙星聯閤後阿米卡星的選擇指數為4。在臨床株,環丙沙星聯閤CCCP後選擇指數較單藥顯著降低。結論除阿米卡星外,美囉培南、頭孢他啶、環丙沙星聯閤EPI可明顯降低MIC及MPC,環丙沙星聯閤CCCP可縮小突變選擇窗,有利于減少耐藥突變體的產生。
목적:탐토항균약연합외배빙억제제( EPI)대동록가단포균내약돌변선택창적영향。방법선택동록가단포균표준주,측정미라배남、두포타정、아미잡성、배병사성4충약물단약최저억균농도( MIC);기반격법측정연합리혈평、오미랍서、아기매소、탄기청화물간록분종( CCCP )、분병안산-정안산-β-내알(PAβN)5충EPI항균약물적MIC。경지평판이배희석법측정항균약물단약이급연합EPI적방내약돌변농도(MPC),계산상응적선택지수(MPC/MIC);분별측정미라배남、두포타정、배병사성연합아미잡성,아미잡성연합배병사성후적선택지수。재림상주중검측미라배남、두포타정、아미잡성、배병사성단약급여CCCP연합후적MIC、MPC급선택지수。결과재표준주,미라배남、두포타정、아미잡성、배병사성단약적선택지수분별위>32,>32,16,16;여리혈평연합후선택지수분별위16、16、16、8;여오미랍서연합후분별위16、32、16、8;여아기매소연합후분별위8、16、16、8;여CCCP연합후분별위8、8、16、8;여PAβN연합후분별위8、16、16、8。미라배남、두포타정、배병사성분별여아미잡성연합후적선택지수위4、4、8。아미잡성여배병사성연합후아미잡성적선택지수위4。재림상주,배병사성연합CCCP후선택지수교단약현저강저。결론제아미잡성외,미라배남、두포타정、배병사성연합EPI가명현강저MIC급MPC,배병사성연합CCCP가축소돌변선택창,유리우감소내약돌변체적산생。
Objective To explore the effects of antibiotics plus efflux pump ( EPI ) inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro.Methods In standard strains , the minimum inhibitory concentrations ( MICs ) of meropenem , ceftazidime , amikacin and ciprofloxacin alone were measured.Then the MICs of four antibiotics respectively plus EPI , including reserpine , omeprazole , azithromycin, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) and Phe-Arg-β-naphtylamide (PAβN), were measured by checkerboard test.And the mutant prevention concentrations ( MPC) of antibiotics alone and antibiotics plus different EPIs were also measured by agar dilution method.Selection indices ( SI) were acquired through MPC divided by MIC.Similarly, the SI of meropenem , ceftazidime and ciprofloxacin which respectively plus amikacin and amikacin plus ciprofloxacin were measured.In clinical strains, MIC, MPC and SI of antibiotics alone and four antibiotics plus CCCP were measured.Results In standard strains , the SI of meropenem, ceftazidime, amikacin and ciprofloxacin alone were >32, >32, 16 and 16.After adding EPI, the SI of four antibiotics were 16, 16, 16, 8 (reserpine), 16, 32, 16, 8 (omeprazole), 8, 16, 16, 8 (azithromycin), 8, 8, 16, 8 (CCCP) and 8, 16, 16, 8 (PAβN).The SI of meropenem, ceftazidime and ciprofloxacin plus amikacin were 4, 4, 8.And the SI of amikacin plus ciprofloxacin was 4.In clinical strains, the SI of ciprofloxacin significantly decreased after adding CCCP.Conclusions Both MIC and MPC of meropenem , ceftazidime and ciprofloxacin decreased significantly after adding EPI.The mutant selection window decreased when ciprofloxacin was combined with CCCP.