Fosfomycin: Mechanism and Resistance
Fosfomycin: Mechanism and Resistance
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DOI：
10.1101/cshperspect.a025262
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发表时间：
2017-02-01
影响因子：
5.4
通讯作者：
Silver, Lynn L.
中科院分区：
文献类型：
--
作者：
Silver, Lynn L.
磷霉素是一种天然产物抗生素，已在西班牙、德国、法国、日本、巴西和南非用于尿路感染（UTI）和其他适应症超过20年，并于1996年在美国注册用于口服治疗粪肠球菌和大肠杆菌引起的非复杂性UTI。它具有广谱性，杀菌性，毒性极低，并作为MurA酶的时间依赖性抑制剂，MurA酶催化肽聚糖合成的第一个关键步骤。尽管对磷霉素的耐药性通过主动转运机制的丧失在体外迅速产生，但在UTI治疗期间很少见到耐药性，似乎是因为耐药生物体的适应性低。最近，在其他适应症中使用磷霉素对抗多药耐药（MDR）病原体的兴趣越来越大，促使美国开发了一种最初用于复杂性UTI的胃肠外制剂。尽管在不复杂的UTI背景下，耐药并不成问题，但随着对其他适应症的扩展，耐药是否仍然存在还有待观察。
Fosfomycin, a natural product antibiotic, has been in use for > 20 years in Spain, Germany, France, Japan, Brazil, and South Africa for urinary tract infections (UTIs) and other indications and was registered in the United States for the oral treatment of uncomplicated UTIs because of Enterococcus faecalis and Escherichia coli in 1996. It has a broad spectrum, is bactericidal, has very low toxicity, and acts as a time-dependent inhibitor of the MurA enzyme, which catalyzes the first committed step of peptidoglycan synthesis. Whereas resistance to fosfomycin arises rapidly in vitro through loss of active transport mechanisms, resistance is rarely seen during therapy of UTIs, seemingly because of the low fitness of the resistant organisms. Recently, interest has grown in the use of fosfomycin against multidrug-resistant (MDR) pathogens in other indications, prompting the advent of development in the United States of a parenteral formulation for use, initially, in complicated UTIs. Whereas resistance has not been problematic in the uncomplicated UTI setting, it remains to be seen whether resistance remains at bay with expansion to other indications.