Helaly Ghada F, Abou Shleib Hamida, Fanaki Nourhan H, Abdel Kader Ola, Ali Ghada H
Dept. of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
J Egypt Public Health Assoc. 2010;85(5-6):247-72.
Fluoroquinolone-resistant Gram-negative pathogens have been increasingly reported from most regions of the world over the last decade. A new plasmid-mediated fluoroquinolone efflux pump gene (qepA) is known to be associated with the 16S rRNA methylase gene (rmtB) that confers resistance to aminoglycosides.
To investigate the potential co-prevalence of qepA and rmtB genes in Escherichia coli (E. coli) clinical isolates collected from Egyptian medical facilities.
A total of 225 non-duplicate E. coli isolates were collected between 2008 and 2009 from two hospitals in Alexandria. Isolates were initially tested for their antibiotic susceptibility by disc diffusion method. Isolates exhibited quinolone and aminoglycosides co-resistance profile were screened for the presence of qepA and rmtB genes. The effect of efflux pump inhibitor, phenylarginine-beta-naphthylamide (PAβN) on the minimum inhibitory concentration (MIC) of ciprofloxacin, levofloxacin and gentamicin against these strains was tested and log activity index was calculated. Using checkerboard titration method, the combinations of gentamicin with ciprofloxacin against the strains harboring qepA and rmtB genes were tested and the fractional inhibitory concentrations (FIC) were calculated.
Forty-five E. coli isolates exhibited quinolone and aminoglycosides co-resistance profile. Of them, two E. coli isolates were positive for qepA, and three harbored rmtB genes. No association between both genes was detected. The calculated log activity index revealed a reduction in MIC of the fluoroquinolones with PAβN but not of gentamicin. FIC calculated here for gentamicin/ciprofloxacin combinations reflected either antagonism or indifference against the strains harboring qepA and rmtB genes.
qepA as well as rmtB genes-carrying E. coli strains could become a greater nosocomial infection problem with appropriate foci of selective pressure. Therefore, public health support for active surveillance for plasmid mediated fluoroquinolones, aminoglycosides resistance determinants among clinical E. coli isolates should be encouraged. In addition, the effect of efflux pumps needs to be considered in the design of future antibiotics as their synergistic role may pave the way to novel combination therapies that could be used against these strains.
在过去十年中，世界上大多数地区对氟喹诺酮耐药的革兰氏阴性病原体的报道日益增多。已知一种新的质粒介导的氟喹诺酮外排泵基因（qepA）与赋予对氨基糖苷类耐药性的16S rRNA甲基化酶基因（rmtB）有关。
调查从埃及医疗机构收集的大肠杆菌临床分离株中qepA和rmtB基因的潜在共流行情况。
2008年至2009年期间，从亚历山大港的两家医院共收集了225株非重复的大肠杆菌分离株。最初采用纸片扩散法检测分离株的抗生素敏感性。对表现出喹诺酮和氨基糖苷类共同耐药谱的分离株进行qepA和rmtB基因的筛查。测试外排泵抑制剂苯基精氨酸-β-萘酰胺（PAβN）对环丙沙星、左氧氟沙星和庆大霉素对这些菌株的最低抑菌浓度（MIC）的影响，并计算对数活性指数。采用棋盘滴定法，测试庆大霉素与环丙沙星对携带qepA和rmtB基因菌株的联合作用，并计算部分抑菌浓度（FIC）。
45株大肠杆菌分离株表现出喹诺酮和氨基糖苷类共同耐药谱。其中，2株大肠杆菌分离株qepA呈阳性，3株携带rmtB基因。未检测到这两个基因之间的关联。计算得到的对数活性指数显示，PAβN可降低氟喹诺酮类药物的MIC，但对庆大霉素无影响。此处计算的庆大霉素/环丙沙星联合用药的FIC反映了对携带qepA和rmtB基因菌株的拮抗或无关作用。
携带qepA以及rmtB基因的大肠杆菌菌株在存在适当选择压力源的情况下可能会成为更严重的医院感染问题。因此，应鼓励公共卫生部门积极监测临床大肠杆菌分离株中质粒介导的氟喹诺酮、氨基糖苷类耐药决定因素。此外，在未来抗生素的设计中需要考虑外排泵的作用，因为它们的协同作用可能为针对这些菌株的新型联合疗法铺平道路。
