Imipenem/cilastatin/relebactam: A new carbapenem β-lactamase inhibitor combination. (13th February 2021)

• Record Type: Journal Article
• Authors: Mansour, Hanine; Ouweini, Ahmad E L; Chahine, Elias B; Karaoui, Lamis R
• Is Part Of: American journal of health-system pharmacy. Volume 78:Number 8(2021)
• Page Start: 674
• Page End: 683
• Publication Date: 2021-02-13
• Subjects: β-lactam/β-lactamase inhibitor -- imipenem/cilastatin -- intraabdominal infection -- pneumonia -- relebactam -- urinary tract infection; Hospital pharmacies -- United States -- Periodicals; 615.1
• DOI: 10.1093/ajhp/zxab012
• Languages: English
• ISSNs: 1079-2082

Abstract

Abstract: Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of imipenem/cilastatin/relebactam are reviewed. Summary: 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. Conclusion: 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.