Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World.

Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World.
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新型眼科抗菌药物组合对来自世界各地的大量金黄色葡萄球菌临床眼部分离株的功效。

DOI:
10.1097/ico.0000000000002414
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发表时间:
2020
期刊:
影响因子:
2.8
通讯作者:
Wozniak,RachelAF
Wozniak,RachelAF
中科院分区:
医学3区
文献类型:
--
作者:
Laskey,Emily;Chen,Yimin;Sohn,MichaelB;Gruber,Emma;Chojnacki,Michaelle;Wozniak,RachelAF

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目的:金黄色葡萄球菌是导致角膜炎的主要原因,需要紧急抗菌治疗。然而,不断增加的抗生素耐药性使目前的眼科抗生素越来越无效。首先,对一组不同的金黄色葡萄球菌对6种常用眼科抗生素的耐药性进行了评估。接下来,一种新近发现的含有多粘菌素B/甲氧嘧啶(PT)+利福平的抗菌药物组合在体外和体内研究中对金黄色葡萄球菌都表现出了令人印象深刻的效果,通过测试该组合对临床菌株的疗效,评估了该组合作为潜在的角膜炎治疗药物的潜力。测定所有菌株对莫西沙星、左氧氟沙星、万古霉素、红霉素、妥布霉素、利福平和PT的最低抑菌浓度,以确定当代临床分离株对当前治疗方案的耐药率,并与PT+利福平的耐药率进行比较。结果:在所测试的163株分离菌中,对红霉素(69%)、莫西沙星(33%)、左氧氟沙星(40%)和妥布霉素(17%)耐药率较高。相反,包括多重耐药菌株在内的整个菌株对PT+利福平都是敏感的,这表明了这种组合的有效性。结论:我们证实了金黄色葡萄球菌临床分离株中普遍存在抗生素耐药性,这突显了人们对当前眼科抗生素有效性的担忧。然而,PT+利福平的药物组合可100%根除测试菌株,表明有能力克服现有的循环耐药因素,因此,可能是一种有希望的金黄色葡萄球菌角膜炎的治疗方法。
Purpose:Staphylococcus aureus is a leading cause of keratitis requiring urgent antimicrobial treatment. However, rising antibiotic resistance has rendered current ophthalmic antibiotics increasingly ineffective. First, a diverse, ocular S. aureus strain set was evaluated for resistance to 6 commonly used ophthalmic antibiotics. Next, a recently discovered antimicrobial drug combination containing polymyxin B/trimethoprim (PT)+ rifampin that displayed impressive efficacy toward S. aureus in both in vitro and in vivo studies was evaluated as a potential novel keratitis therapeutic through testing this combination's efficacy against the clinical strain set.Methods:A total of 163 S. aureus isolates were collected either commercially or from the Flaum Eye Institute, University of Rochester. The minimum inhibitory concentrations of moxifloxacin, levofloxacin, vancomycin, erythromycin, tobramycin, rifampin, and PT were determined for the entire strain set to establish the incidence of resistance to current treatment options among a contemporary clinical isolate set and compared with the performance of PT+ rifampin.Results:Among all 163 isolates tested, high rates of antibiotic resistance were found toward erythromycin (69% resistance), moxifloxacin (33%), levofloxacin (40%), and tobramycin (17%). Conversely, the entire strain set, including multidrug resistant isolates, was sensitive to PT+ rifampin, demonstrating the potency of this combination.Conclusions:We established that antibiotic resistance is pervasive among clinical S. aureus isolates, underscoring the concern for the effectiveness of current ophthalmic antibiotics. The drug combination of PT+ rifampin, however, eradicated 100% of isolates tested, demonstrating the ability to overcome existing circulating resistance factors, and as such, might represent a promising therapeutic for S. aureus keratitis.
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