Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Institute of Wound Research, Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Int J Antimicrob Agents. 2017 Feb;49(2):247-251. doi: 10.1016/j.ijantimicag.2016.10.017. Epub 2016 Dec 6.
Bacterial biofilms are surface-attached communities of slow-growing or non-replicating bacteria tolerant to conventional antibiotic therapies. Although biofilms are known to occur in ca. 80% of all bacterial infections, no therapeutic agent has been developed to eradicate bacteria housed within biofilms. We have discovered that nitroxoline, an antibacterial agent used to treat urinary tract infections, displays broad-spectrum biofilm-eradicating activities against major human pathogens, including drug-resistant Staphylococcus aureus and Acinetobacter baumannii strains. In this study, the effectiveness of nitroxoline to eradicate biofilms was determined using an in vitro [minimum biofilm eradication concentration (MBEC) = 46.9 µM against A. baumannii] and ex vivo porcine skin model (2-3 log reduction in viable biofilm cells). Nitroxoline was also found to eradicate methicillin-resistant S. aureus (MRSA) persister cells in non-biofilm (stationary) cultures, whereas vancomycin and daptomycin were found to be inactive. These findings could lead to effective, nitroxoline-based therapies for biofilm-associated infections.
细菌生物膜是一种附着于表面的群落,由生长缓慢或不复制的细菌组成,能够耐受传统的抗生素治疗。尽管已知生物膜存在于大约 80%的所有细菌感染中,但尚未开发出能够消灭生物膜内细菌的治疗剂。我们发现,用于治疗尿路感染的抗菌药物硝呋太尔对包括耐甲氧西林金黄色葡萄球菌和鲍曼不动杆菌在内的主要人类病原体具有广谱的生物膜清除活性。在这项研究中,使用体外[最低生物膜清除浓度 (MBEC) = 46.9 μM 对抗鲍曼不动杆菌]和离体猪皮模型(对活生物膜细胞的 2-3 对数减少)来确定硝呋太尔消除生物膜的有效性。还发现硝呋太尔可以消除耐甲氧西林金黄色葡萄球菌(MRSA)非生物膜(静止)培养物中的持久性细胞,而万古霉素和达托霉素则没有活性。这些发现可能为生物膜相关感染提供有效的硝呋太尔为基础的治疗方法。