Department of Clinical Pharmacy, College of Pharmacy, King Abdulaziz University, P.O. Box 80200, Jeddah, 21589, Saudi Arabia.
Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
Drugs. 2019 Feb;79(3):243-269. doi: 10.1007/s40265-019-1054-3.
Plazomicin is a novel semisynthetic parenteral aminoglycoside that inhibits bacterial protein synthesis. It was approved by the United States Food and Drug Administration for use in adults with complicated urinary tract infections (cUTI), including pyelonephritis. Plazomicin displays potent in vitro activity against Enterobacteriaceae, including both extended-spectrum β-lactamase-producing and carbapenem-resistant isolates. Plazomicin's enhanced Enterobacteriaceae activity is due to its stability to commonly encountered aminoglycoside-modifying enzymes that compromise the activity of traditional aminoglycosides. Plazomicin resistance in Enterobacteriaceae is via modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases. Plazomicin does not display improved activity over traditional aminoglycosides against other problematic resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter baumannii. Plazomicin has been assessed in two phase III randomized controlled trials. The EPIC trial compared plazomicin and meropenem for the management of cUTI. In this trial, plazomicin demonstrated superiority in composite cure (81.7% vs 70.1%; difference 11.6%; 95% confidence interval [CI] 2.7-25.7) at the test-of-cure visit, which was driven by enhanced sustained microbiological eradication. The CARE trial compared plazomicin-based and colistin-based combinations in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE). In this analysis, plazomicin-based combinations were associated with numerically decreased mortality or serious disease-related complications when compared with colistin-based combinations (23.5% vs 50%, respectively; 90% CI -0.7 to 51.2). Furthermore, plazomicin was also associated with a lower incidence of nephrotoxicity than colistin. However, small sample sizes limit the interpretation of the findings in the CARE trial. Plazomicin is a novel aminoglycoside that offers clinicians an additional option for the management of CRE infections, with superior activity compared with traditional aminoglycosides and potentially improved efficacy and decreased toxicity compared with colistin.
硫酸普拉唑米辛是一种新型半合成的氨基糖苷类药物，可抑制细菌蛋白质合成。它已获得美国食品和药物管理局批准，用于治疗成人复杂性尿路感染（cUTI），包括肾盂肾炎。硫酸普拉唑米辛对肠杆菌科具有强大的体外活性，包括产生超广谱β-内酰胺酶和耐碳青霉烯的分离株。硫酸普拉唑米辛对肠杆菌科的增强活性是由于其对常见氨基糖苷修饰酶的稳定性，这些酶会削弱传统氨基糖苷类药物的活性。肠杆菌科对硫酸普拉唑米辛的耐药性是由于核糖体结合位点的修饰，这是由于 16S rRNA 甲基转移酶的表达所致。硫酸普拉唑米辛对其他有问题的耐药革兰氏阴性菌，即铜绿假单胞菌和鲍曼不动杆菌，没有显示出比传统氨基糖苷类药物更好的活性。硫酸普拉唑米辛已在两项 III 期随机对照试验中进行了评估。EPIC 试验比较了硫酸普拉唑米辛和美罗培南治疗复杂性尿路感染。在这项试验中，硫酸普拉唑米辛在治疗结束时的复合治愈率（81.7%对 70.1%；差异 11.6%；95%置信区间[CI]为 2.7%至 25.7%）方面具有优势，这是由于持续的微生物清除率提高所致。CARE 试验比较了基于硫酸普拉唑米辛和多粘菌素的组合在患有耐碳青霉烯肠杆菌科（CRE）严重感染的患者中的疗效。在这项分析中，与基于多粘菌素的组合相比，基于硫酸普拉唑米辛的组合与死亡率或严重疾病相关并发症的发生率降低有关（分别为 23.5%对 50%；90%CI-0.7 至 51.2%）。此外，与多粘菌素相比，硫酸普拉唑米辛也与较低的肾毒性发生率相关。然而，小样本量限制了 CARE 试验结果的解释。硫酸普拉唑米辛是一种新型氨基糖苷类药物，为临床医生提供了一种治疗 CRE 感染的额外选择，与传统氨基糖苷类药物相比具有更强的活性，与多粘菌素相比可能具有更好的疗效和降低的毒性。
