Ventura Roberta F, Galdino Anna Clara M, Viganor Livia, Schuenck Ricardo P, Devereux Michael, McCann Malachy, Santos André L S, Nunes Ana Paula F
Department of Pathology, Federal University of Espírito Santo, Espírito Santo, Brazil.
Infection Diseases Post-Graduation Program, Federal University of Espírito Santo, Espírito Santo, Brazil.
Braz J Microbiol. 2020 Dec;51(4):1703-1710. doi: 10.1007/s42770-020-00351-9. Epub 2020 Jul 31.
Therapeutic options are limited for patients infected with Acinetobacter baumannii due to its multidrug-resistance profile. So, the search for new antimicrobials against this gram-negative bacterial pathogen has become a worldwide priority. The present study aimed to evaluate the effects of 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)]ClO (Ag-phendione) and Cu(phendione)·4HO (Cu-phendione) on 26 carbapenemase-producing A. baumannii strains. The susceptibility to carbapenems was performed by detecting the metallo-beta-lactamase (MBL) genes by PCR and by determining the MIC. Also, disk diffusion method was applied to evaluate the susceptibility to other antimicrobial classes. The test compounds were evaluated on both planktonic- and biofilm-growing bacterial cells. The results revealed that all A. baumannii strains had the intrinsic bla gene, and at least one of the bla or bla genes. The geometric mean MIC and minimum bactericidal concentration (MBC) values, respectively, were as follows: Cu-phendione (1.56 and 2.30 μM), Ag-phendione (2.48 and 3.63 μM), phendione (9.44 and 9.70 μM), and phen (70.46 and 184.28 μM). The test compounds (at 0.5 × MIC) affected the biofilm formation and disrupted the mature biofilm, in a typically dose-dependent manner, reducing biomass and viability parameters. Collectively, silver and copper-phendione derivatives presented potent antimicrobial action against planktonic- and biofilm-forming cells of carbapenemase-producing A. baumannii.
由于鲍曼不动杆菌具有多重耐药性,感染该菌的患者治疗选择有限。因此,寻找针对这种革兰氏阴性细菌病原体的新型抗菌药物已成为全球的优先事项。本研究旨在评估1,10-菲咯啉(菲咯啉)、1,10-菲咯啉-5,6-二酮(菲咯啉二酮)、[Ag(菲咯啉二酮)]ClO(银-菲咯啉二酮)和Cu(菲咯啉二酮)·4H₂O(铜-菲咯啉二酮)对26株产碳青霉烯酶鲍曼不动杆菌菌株的影响。通过PCR检测金属β-内酰胺酶(MBL)基因并测定MIC来检测对碳青霉烯类药物的敏感性。此外,采用纸片扩散法评估对其他抗菌药物类别的敏感性。对浮游菌和生物膜生长的细菌细胞均进行了受试化合物的评估。结果显示,所有鲍曼不动杆菌菌株均具有固有bla基因,以及bla或bla基因中的至少一种。几何平均MIC和最低杀菌浓度(MBC)值分别如下:铜-菲咯啉二酮(1.56和2.30 μM)、银-菲咯啉二酮(2.48和3.63 μM)、菲咯啉二酮(9.44和9.70 μM)以及菲咯啉(70.46和184.28 μM)。受试化合物(在0.5×MIC浓度下)以典型的剂量依赖性方式影响生物膜形成并破坏成熟生物膜,降低生物量和活力参数。总体而言,银和铜-菲咯啉二酮衍生物对产碳青霉烯酶鲍曼不动杆菌的浮游菌和生物膜形成细胞具有强大的抗菌作用。