泛耐药铜绿假单胞菌对β内酰胺类抗生素的耐药机制研究

Examination of the mechanism of β-lactam resistance in pan-drug resistant Pseudomonas aeruginosa

目的探讨泛耐药(pan-drug resistant,PDR)铜绿假单胞菌对β内酰胺类抗生素的耐药机制。方法以相应方法分别检测PDR铜绿假单胞菌对β内酰胺类抗生素的主要耐药机制:常见β内酰胺酶的表达,膜孔蛋白OprD的缺失,及耐药结节分化家族(RND)主动外排系统的激活。结果 20株PDR铜绿假单胞菌中,可检出的产β内酰胺酶的菌株16株(80%):产AmpCs酶菌株16株(80%),其中产超广谱AmpCs酶(extended-spectrum AmpCβ-lactamases,ESACs)12株(60%),产ES-BLs菌株14株(70%),产金属β内酰胺酶(MBLs)1株(5%);膜孔蛋白OprD呈不同程度缺失的菌株11株(55%);主动外排系统中MexA-MexB-OprM、MexC-MexD-OprJ、MexE-MexF-OprN、MexX-MexY-OprM呈过度激活的菌株分别为5株(25%)、3株(15%)、4株(20%)、1株(5%)。65%PDR铜绿假单胞菌存在2种或2种以上耐药机制,以高产β内酰胺酶合并膜孔蛋白OprD缺失最多见。结论高产AmpCs和(或)ESBLs,合并膜孔蛋白OprD的缺失或主动外排泵的激活,是PDR铜绿假单胞菌对β内酰胺类抗生素的主要耐药机制。

Objective To explore the mechanism of β-lactam resistance in pan drug resistant （PDR） P. aeruginosa. Methods The primary mechanism of resistance to β-lactams was analyzed, including the expression of common β- lactamases, loss of OprD and overexpression of RND active efflux systems in PDR P. aeruginosa isolates. Results of the 20 PDR P. aeruginosa strains, 16（80%）strains expressed β-lactamases, 16 （80%） expressed AmpCs, including 12 （60%） with ESACs, 14 （70%） expressed ESBLs, 1 （5%） expressed MBLs. Furthermore, 11 （55%） of the 20 ostrains lost OprD,5 （25%） overexpressed MexA-MexB-OprM, 3 （15%） showed overexpression of MexC-MexD-OprJ, 4 （20%） overexpressed MexE-MexF-OprN, 1 （5%） had overexpression of MexX-MexY OprM. At least 2 types of resistance mechanism were identified in 65% of the PDR P. aeruginosa strains. Coexistence of β-lactamases overproduction and loss of porin OprD was the most common combination. Conclusions Overexpression of AmpCs and/or ESBLs,together with loss of OprDor overexpression of active efflux systems is the main mechanism of β-lactam resistance in PDR P. aeruginosa strains.