Tohidpour Abolghasem, Najar Peerayeh Shahin, Mehrabadi Jalil F, Rezaei Yazdi Hadi
Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, Jalal al ahmad street, P.O. Box 14115-111, Tehran, Iran.
Curr Microbiol. 2009 Sep;59(3):352-5. doi: 10.1007/s00284-009-9444-5. Epub 2009 Jun 25.
In gram negative bacteria, fluoroquinolone resistance is acquired by target mutations in topoisomerase genes or by reducing the permeation of drugs due to the increase in expression of endogenous multidrug efflux pumps that expel structurally unrelated antimicrobial agents. An ongoing challenge is searching for new inhibitory substances in order to block efflux pumps and restore the antibiotic drugs susceptibility. In this research, we sought to investigate the interplay between ciprofloxacin and an efflux pump inhibitor (EPI), phenyl alanine arginyl beta-naphtylamide (PAbetaN), to determine the prevalence of efflux pump overexpression in clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was tested at different concentrations (256-0.25 microg/ml) with a fixed concentration of PAbetaN (50 microg/ml). The isolates susceptibility profiles were analyzed by disc diffusion and agar dilution methods using 10 antibiotic discs and 4 powders. It was found that in the presence of PAbetaN, resistance to ciprofloxacin was inhibited obviously and MIC values were decreased. The comparison between subgroups of P. aeruginosa isolates with different resistance profiles indicates that efflux pump overexpression (EPO) is present in 35% of ciprofloxacin resistant isolates with no cross resistance and in variable frequencies among isolates showing cross resistance to other tested antibiotics: gentamicin (31%), ceftazidime (29%), and imipenem (18%). Altogether, these results imply that PAbetaN maybe effective to restore the fluoroquinolone drugs susceptibility in clinical treatment procedures. Results also show that increased use of a fluoroquinolone drug such as ciprofloxacin can affect the susceptibility of P. aeruginosa to other different antipseudomonal agents.
在革兰氏阴性菌中，氟喹诺酮耐药性是通过拓扑异构酶基因的靶点突变获得的，或者是由于内源性多药外排泵的表达增加导致药物渗透减少而产生的，这些外排泵可排出结构不相关的抗菌剂。当前的一项挑战是寻找新的抑制物质，以阻断外排泵并恢复抗生素药物的敏感性。在本研究中，我们试图研究环丙沙星与一种外排泵抑制剂（EPI）苯丙氨酸精氨酰β-萘酰胺（PAbetaN）之间的相互作用，以确定铜绿假单胞菌临床分离株中外排泵过表达的发生率。环丙沙星在不同浓度（256 - 0.25微克/毫升）下与固定浓度的PAbetaN（50微克/毫升）一起进行测试。使用10种抗生素纸片和4种粉剂，通过纸片扩散法和琼脂稀释法分析分离株的药敏谱。结果发现，在PAbetaN存在的情况下，对环丙沙星的耐药性明显受到抑制，最低抑菌浓度（MIC）值降低。对具有不同耐药谱的铜绿假单胞菌分离株亚组进行比较表明，在35%对环丙沙星耐药且无交叉耐药的分离株中存在外排泵过表达（EPO），在对其他测试抗生素（庆大霉素，31%；头孢他啶，29%；亚胺培南，18%）表现出交叉耐药的分离株中，其频率各不相同。总之，这些结果表明PAbetaN在临床治疗过程中可能有效地恢复氟喹诺酮类药物的敏感性。结果还表明，增加使用环丙沙星等氟喹诺酮类药物会影响铜绿假单胞菌对其他不同抗假单胞菌药物的敏感性。
