a Spero Therapeutics , Cambridge , MA , USA.
Expert Rev Anti Infect Ther. 2018 Jul;16(7):513-522. doi: 10.1080/14787210.2018.1496821. Epub 2018 Jul 27.
Infections caused by antibiotic-resistant pathogens, particularly Gram-negative bacteria, have become increasingly challenging to successfully treat. The beta-lactam antibiotic subclass, the carbapenems, have proven valuable for the treatment of such Gram-negative bacterial infections due to their spectrum and β-lactamase stability properties. However, all marketed carbapenems to date are parenterally administered to adult patients. Areas covered: One carbapenem, tebipenem-pivoxil (TBPM-PI), is an oral prodrug that was approved in Japan for pediatric use only in 2009. This review summarizes preclinical and clinical data for TBPM-PI, which is now in clinical development again this time for use as the first oral carbapenem available for treatment of bacterial infections in adult patients. Expert commentary: There is an urgent unmet need with an increasing prevalence of fluoroquinolone-resistant and ESBL-producing Gram-negative pathogens in the hospital and community setting. Carbapenems have traditionally been considered the drugs of choice for infections caused by enterobacteria producing ESBL and AmpC enzymes because they are not affected by these resistance mechanisms. The carbapenem, TBPM-PI, offers an oral option, particularly as step-down therapy, for use of this class in the treatment of serious Gram-negative infections.
由抗生素耐药病原体引起的感染,特别是革兰氏阴性菌感染,越来越难以成功治疗。β-内酰胺类抗生素亚类中的碳青霉烯类抗生素由于其广谱性和β-内酰胺酶稳定性而被证明对治疗此类革兰氏阴性菌感染非常有效。然而,迄今为止,所有上市的碳青霉烯类抗生素均为注射用药物,用于治疗成人患者。
一种碳青霉烯类抗生素,替比培南匹伏酯(TBPM-PI),是一种口服前体药物,仅在 2009 年在日本获得批准用于儿科。这篇综述总结了 TBPM-PI 的临床前和临床数据,目前它正在重新进行临床试验,将作为第一种可用于治疗成人细菌感染的口服碳青霉烯类抗生素使用。
在医院和社区环境中,氟喹诺酮类耐药和产 ESBL 的革兰氏阴性病原体的流行率不断上升,这方面存在着迫切的未满足的需求。碳青霉烯类抗生素通常被认为是治疗产 ESBL 和 AmpC 酶的肠杆菌引起的感染的首选药物,因为它们不受这些耐药机制的影响。碳青霉烯类抗生素 TBPM-PI 为治疗严重革兰氏阴性感染提供了一种口服选择,特别是作为降阶梯治疗的选择。