携qnrA基因肠杆菌科细菌的耐药性及其分子机制研究

Antimicrobial Agents Resistance and Its Molecular Mechanisms of Clinical Isolates of Enterobacteriaceae with qnrA

目的了解质粒定位的喹诺酮类耐药基因qnrA在肠杆菌科细菌中的发生率、耐药表型特征及其分子机制。方法收集2003-2004年深圳地区临床分离的肠杆菌科细菌332株,采用引物特异性PCR结合测序识别qnrA阳性株、gyrA和parC基因耐药变异及超广谱β-内酰胺酶(ESBLs)或AmpC酶基因;K-B法、琼脂倍比稀释法和E-test法进行qnrA阳性株的药敏检测,表型确认实验识别产ESBLs细菌。结果qnrA阳性株的总检出率为3.9%,以阴沟肠杆菌(15.6%)为高;qnrA阳性株具有多重耐药的特征,多数伴产ESBLs并存在gyrA及parC基因的耐药变异;qnrA基因定位在Sul1型Ⅰ类整合子In37或InX上。结论质粒定位的qnrA基因,是导致肠杆菌科细菌对喹诺酮类抗菌药物产生耐药的重要原因,其潜在的水平传播能力及多重耐药的遗传学背景,是临床抗感染治疗的严峻挑战。

OBJECTIVE To determine the prevalence of gene qnrA in clinical isolates of Enterobacteriaceae, phenotypes of drug resistance and their molecular mechanisms. METHODS Totally 332 isolates of Enterobacteriaceae from Shenzhen City from 2003 to 2004 were screened for the presence of qnrA by PCR. The gyrA, and parC genes the genes, coding ESBLs and AmpC were amplified and sequenced. K-B method, the international standard plate dilute method and E-test were used to detect MIC of the isolates with qnrA. ESBLs were distinguished by the phenotypic confirmatory test. RESULTS The incidence of qnrA in clinical isolates was 3.9%, the highest incidence of 15.6% occurred in Enterobacter cloacae. The clinical isolates were multi-resistant. gyrA And parC mutation associated with quinolone resistance and ESBLs producing was confirmed in most of the isolates with qnrA. qnrA Was embedded in In37 or InX classified to Sull type class Ⅰ integrons. CONCLUSIONS Gene qnrA located in plasmids is an important mechanism mediated quinolone resistance in Enterobacteriaceae. The potential horizontal transferability and multiple resistance hereditary background in these isolates challenge the anti-infective therapy.