泵抑制剂对诱导产ESBLs鸡大肠杆菌抗菌药物敏感性的影响

目的:探讨头孢曲松、头孢噻肟、头孢噻呋诱导鸡源大肠杆菌耐药产ESBLs与主动外排机制的关系。方法:用头孢曲松、头孢噻肟、头孢噻呋诱导3株临床分离菌和标准菌O78至产ESBLs;采用琼脂二倍稀释法观察外排泵抑制剂利血平和CCCP对诱导菌抗菌药物敏感性的影响。结果:加入利血平后,头孢曲松诱导后的菌株,阿米卡星、氟苯尼考、磷霉素组的MIC值变化有统计学差异,耐药率下降范围为25%～75%;头孢噻肟诱导后的菌株,头孢曲松、头孢噻呋、多西环素、氟苯尼考、磷霉素组MIC值变化有统计学差异,耐药率下降为25%～100%;头孢噻呋诱导后的菌株,其中头孢曲松、头孢噻呋、阿米卡星、氟苯尼考、磷霉素有统计学差异,耐药率下降为25%～100%。加入CCCP以后,仅头孢噻肟诱导后的菌株,头孢曲松MIC值变化差异显著;头孢噻呋诱导的菌株,头孢曲松、氟苯尼考差异显著;且耐药率下降范围均为25%～75%;利血平与抗菌药物合用后对诱导菌抗菌药物敏感性的影响高于CCCP。结论:3种头孢类药物诱导后的菌株对10种抗菌药物的外排表型存在差异;鸡大肠杆菌特异性耐药机制ESBLs可激活非特异性耐药机制外排表型的过度表达。

Effect of Efflux Pump Inhibitor on Sensitivity of Induced Positive ESBLs Escherichia coli from Chickens to Antibacterial Drugs

Objective: To investigate the role of ceftriaxone,cefotaxime and ceftiofur in inducing Escherichia coli to produce ESBLs,and the mechanism of efflux pump inhibitor in positive ESBLs Escherichia coli.Methods: Using different concentrations of ceftriaxone,cefotaxime and ceftiofur to induce 3 clinical isolates of Escherichia coli and O78 to exhibit multidrug-resistant phenotypes in vitro.After inducement,they showed positive ESBLs.Then the effects of efflux pump on the sensitivity of the induced bacteria to ten kinds of antibacterial drugs were measured by agar 2 times-dilution method.Results: After being treated with efflux pump inhibitor reserpine,the MICs of amikacin,florfenicol and fosfomycin had statistical difference,and the decline range of antimicrobial resistance was from 25% to 75% in ceftriaxone-induced bacteria;the MICs of ceftriaxone,ceftiofur,doxycycline,florfenicol and fosfomycin had statistical difference,and the decline range of antimicrobial resistance was from 25% to 100% in cefotaxime-induced bacteria;the MICs of ceftriaxone,ceftiofur,amikacin,florfenicol and fosfomycin had statistical difference,and the decline range of antimicrobial resistance was from 25% to 100% in ceftiofur-induced bacteria.After adding CCCP,the MICs of ceftriaxone had statistical difference in cefotaxime-induced bacteria;the MICs of ceftriaxone and florfenicol had statistical difference in cefotaxime-induced bacteria,the decline range of two antimicrobial resistance was from 25% to 75%.Conclusion: The effects of efflux pump on the sensitivity of three-cephalosporin-drug-induced strains against ten kinds of antibacterial drugs were different,the role of reserpine was higher than that of CCCP,ESBLs could activate the efflux pump.