Department of Internal Medicine/Sunrise Health GME Consortium, MountainView Hospital, Las Vegas, Nevada, USA.
Department of Pharmacy, MountainView Hospital, Las Vegas, Nevada, USA.
Pharmacotherapy. 2021 Sep;41(9):748-761. doi: 10.1002/phar.2614. Epub 2021 Aug 17.
Tebipenem pivoxil hydrobromide is a novel orally bioavailable prodrug of tebipenem, a carbapenem antimicrobial, that binds to penicillin-binding proteins, inhibiting the synthesis of the bacterial cell wall. This results in weakening of peptidoglycan, leading to lysis of bacterial cells. Tebipenem displays a broad spectrum of activity against anaerobic, gram-positive, and gram-negative pathogens, including extended-spectrum β-lactamase producing Enterobacterales. In a large phase 3 clinical trial (ADAPT-PO), oral tebipenem pivoxil hydrobromide 600 mg every 8 h was shown to be non-inferior to intravenous ertapenem 1 g every 24 h. Overall response at test of cure was 58.8% [264/449] in the tebipenem pivoxil hydrobromide group compared to 61.6% [258/419] in the ertapenem group for the treatment of complicated urinary tract infections, including acute pyelonephritis. At the test of cure, clinical cure rates were 93.1% and 93.6% and microbiological eradication was 59.5% and 63.5% with tebipenem pivoxil hydrobromide and ertapenem, respectively. The most common adverse reactions associated with tebipenem pivoxil hydrobromide are diarrhea, headache, and nausea. As with other carbapenems, tebipenem pivoxil hydrobromide is expected to have the potential to decrease the seizure threshold and will likely require renal dosage adjustment for patients with altered renal function due to high renal clearance. If approved in the United States, tebipenem pivoxil hydrobromide can serve as a potential oral antimicrobial option to decrease hospital length of stay and prevent hospital admissions due to resistant pathogens.
盐酸特比培南匹伏酯是一种新型的可口服生物利用的替比培南前药，替比培南是一种碳青霉烯类抗菌药物，与青霉素结合蛋白结合，抑制细菌细胞壁的合成。这导致肽聚糖减弱，导致细菌细胞裂解。特比培南对厌氧、革兰阳性和革兰阴性病原体具有广泛的活性，包括产生超广谱β-内酰胺酶的肠杆菌科。在一项大型 3 期临床试验（ADAPT-PO）中，口服特比培南匹伏酯 600mg 每 8 小时与静脉注射厄他培南 1g 每 24 小时相比，显示非劣效性。在治疗复杂性尿路感染（包括急性肾盂肾炎）时，特比培南匹伏酯组的总治愈率为 58.8%[449 例中的 264 例]，而厄他培南组为 61.6%[419 例中的 258 例]。在治愈测试时，特比培南匹伏酯组的临床治愈率为 93.1%，微生物清除率为 59.5%，厄他培南组的临床治愈率为 93.6%，微生物清除率为 63.5%。与特比培南匹伏酯相关的最常见不良反应是腹泻、头痛和恶心。与其他碳青霉烯类药物一样，特比培南匹伏酯预计有降低癫痫发作阈值的潜力，并且由于高肾清除率，可能需要对肾功能改变的患者进行肾剂量调整。如果在美国获得批准，特比培南匹伏酯可作为一种潜在的口服抗菌药物选择，以减少住院时间并预防因耐药病原体导致的住院。
