Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
BacterioScan, St. Louis, Missouri, USA.
Antimicrob Agents Chemother. 2018 Dec 21;63(1). doi: 10.1128/AAC.01929-18. Print 2019 Jan.
and are two of the most common causes of bacterial keratitis and corresponding corneal blindness. Accordingly, such infections are predominantly treated with broad-spectrum fluoroquinolones, such as moxifloxacin. Yet, the rising fluoroquinolone resistance has necessitated the development of alternative therapeutic options. Herein, we describe the development of a polymyxin B-trimethoprim (PT) ophthalmic formulation containing the antibiotic rifampin, which exhibits synergistic antimicrobial activity toward a panel of contemporary ocular clinical and isolates, low spontaneous resistance frequency, and bactericidal kinetics and antibiofilm activities equaling or exceeding the antimicrobial properties of moxifloxacin. The PT plus rifampin combination also demonstrated increased efficacy in comparison to those of either commercial PT or moxifloxacin in a murine keratitis model of infection, resulting in bacterial clearance of 70% in the animals treated. These results suggest that the combination of PT and rifampin may represent a novel antimicrobial agent in the treatment of bacterial keratitis.
和 是细菌性角膜炎和相应角膜盲的两个最常见原因。因此，此类感染主要用广谱氟喹诺酮类药物治疗，如莫西沙星。然而，氟喹诺酮类药物耐药性的上升，需要开发替代治疗方案。在此，我们描述了一种多粘菌素 B-甲氧苄啶（PT）眼用制剂的开发，该制剂含有抗生素利福平，对一组当代眼部临床 和 分离株表现出协同抗菌活性，自发耐药频率低，杀菌动力学和抗生物膜活性与莫西沙星相当或超过其抗菌特性。PT 加利福平联合用药在感染性小鼠角膜炎模型中也显示出比商业 PT 或莫西沙星更高的疗效，使动物治疗中的细菌清除率达到 70%。这些结果表明，PT 和利福平的联合可能代表治疗细菌性角膜炎的一种新型抗菌药物。
