Department of Pharmacy Practice, School of Pharmacy, Lebanese American University, Byblos, Lebanon.
Lebanese American University Medical Center - Rizk Hospital, Beirut, Lebanon.
Am J Health Syst Pharm. 2021 Mar 31;78(8):674-683. doi: 10.1093/ajhp/zxab012.
The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of imipenem/cilastatin/relebactam are reviewed.
Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established β-lactam and a new β-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options. The antibiotic is also indicated for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The antibiotic is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales (CRE) such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-β-lactamase (MBL)-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of imipenem/cilastatin/relebactam was found to be comparable to that of imipenem/cilastatin plus colistin for the treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP/VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with the new antibiotic. The RESTORE-IMI 2 trial demonstrated the noninferiority of imipenem/cilastatin/relebactam to piperacillin/tazobactam for the treatment of HABP/VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension.
Imipenem/cilastatin/relebactam is a new β-lactam/β-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but excluding MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. It is approved for the treatment of cUTIs, cIAIs, and HABP/VABP.
综述亚胺培南/西司他丁/雷巴他定的药理学、药代动力学、药效学、抗菌活性、疗效、安全性和当前监管状况。
亚胺培南/西司他丁/雷巴他定是一种新批准的抗感染药物组合，由一种已广泛使用的β-内酰胺类药物和一种新的β-内酰胺酶抑制剂组成，用于治疗复杂性尿路感染（cUTI），包括肾盂肾炎和复杂性腹腔内感染（cIAI），适用于 18 岁及以上的患者，这些患者有有限或没有其他治疗选择，且对敏感革兰氏阴性菌引起的感染。该抗生素也可用于治疗医院获得性细菌性肺炎（HABP）和呼吸机相关性细菌性肺炎（VABP）。该抗生素在体外对多种病原体具有活性，包括多药耐药（MDR）铜绿假单胞菌和产金属β-内酰胺酶（MBL）的肠杆菌科细菌以及耐碳青霉烯类的鲍曼不动杆菌。雷巴他定的加入并不能恢复亚胺培南对产金属β-内酰胺酶的肠杆菌科细菌和耐碳青霉烯类的鲍曼不动杆菌的活性。进行了两项关于亚胺培南/西司他丁/雷巴他定的 3 期临床试验。在 RESTORE-IMI 1 试验中，与亚胺培南/西司他丁加黏菌素相比，亚胺培南/西司他丁/雷巴他定治疗 HABP/VABP、cUTI 和 cIAI 中由亚胺培南不敏感的革兰氏阴性菌引起的感染的疗效和安全性相当，但新抗生素报告的肾毒性发生率明显较低。RESTORE-IMI 2 试验表明，亚胺培南/西司他丁/雷巴他定治疗 HABP/VABP 的非劣效性优于哌拉西林/他唑巴坦。临床试验中常见的不良反应包括贫血、肝酶升高、电解质失衡、恶心、呕吐、腹泻、头痛、发热、静脉炎和/或输液部位反应以及高血压。
亚胺培南/西司他丁/雷巴他定是一种新的β-内酰胺/β-内酰胺酶抑制剂组合，对 MDR 革兰氏阴性菌具有活性，包括许多 CRE，但不包括产 MBL 的肠杆菌科细菌和耐碳青霉烯类的鲍曼不动杆菌。它被批准用于治疗 cUTI、cIAI 和 HABP/VABP。
