Zhanel George G, Walkty Andrew J, Karlowsky James A
Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, MB, Canada R3A 1R9.
Can J Infect Dis Med Microbiol. 2016;2016:2082693. doi: 10.1155/2016/2082693. Epub 2016 May 10.
Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.
磷霉素是加拿大批准用于治疗成年女性急性单纯性膀胱炎(AUC)的一种新药,适用于感染了对其敏感的大肠埃希菌和粪肠球菌分离株的患者。我们回顾了有关口服磷霉素治疗AUC的文献。对1975年至2015年10月的所有英文参考文献进行了回顾。在加拿大,磷霉素氨丁三醇制成商品名为Monurol®,有3克单剂量的小包装。磷霉素具有独特的化学结构,与β-内酰胺类药物相比,它在更早的位点抑制肽聚糖合成,且与其他药物无交叉耐药性。磷霉素对产超广谱β-内酰胺酶(ESBL)、产AmpC酶、对碳青霉烯类不敏感及多重耐药(MDR)的大肠埃希菌具有广谱抗菌活性。大肠埃希菌对磷霉素的耐药性罕见(<1%)。磷霉素通过肾小球滤过以原形经尿液排泄,单次口服3克后尿药峰浓度约为4000 μg/mL,且在48小时内尿药浓度保持>100 μg/mL。老年患者、孕妇、肾功能或肝功能损害患者均无需调整剂量。磷霉素显示出良好的安全性,临床试验已证明其治疗AUC的疗效与环丙沙星、呋喃妥因和甲氧苄啶-磺胺甲恶唑相当。磷霉素对包括MDR分离株在内的常见尿路病原体的体外活性、包括对孕妇的良好安全性、药物相互作用以及证明其治疗AUC疗效的临床试验数据,已使得加拿大、美国和欧洲的指南/权威机构推荐磷霉素作为治疗AUC的一线药物。