Imipenem/Cilastatin/Relebactam: A Review in Gram-Negative Bacterial Infections

Abstract

Imipenem/cilastatin/relebactam (Recarbrio™) is an intravenously administered combination of the carbapenem imipenem, the renal dehydropeptidase-I inhibitor cilastatin, and the novel β-lactamase inhibitor relebactam. Relebactam is a potent inhibitor of class A and class C β-lactamases, conferring imipenem activity against many imipenem-nonsusceptible strains. Imipenem/cilastatin/relebactam is approved in the USA and EU for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) in adults and other gram-negative infections, including complicated urinary tract infections (cUTIs) [including pyelonephritis] and complicated intra-abdominal infections (cIAIs), in adults with limited or no alternative treatment options. In pivotal phase II and III trials, imipenem/cilastatin/relebactam was noninferior to piperacillin/tazobactam in patients with HABP/VABP and to imipenem/cilastatin in patients with cUTIs and cIAIs. It was also effective in imipenem-nonsusceptible infections. Imipenem/cilastatin/relebactam was generally well tolerated, with a safety profile consistent with that of imipenem/cilastatin. Available evidence indicates that imipenem/cilastatin/relebactam is an effective and generally well tolerated option for gram-negative infections in adults, including critically ill and/or high-risk patients, and a potential therapy for infections caused by carbapenem-resistant pathogens.

Fig. 1

Efficacy of imipenem/cilastatin/relebactam in RESTORE-IMI 2 in adults with hospital-acquired or ventilator-associated bacterial pneumonia [53]. ^†Noninferior to PIP/TAZ as the upper limit of the 2-sided 95% CI for the adjusted treatment difference did not exceed 10%, ^‡Noninferior to PIP/TAZ as the lower limit of the 2-sided 95% CI for the adjusted treatment difference was greater than − 12.5%. IMI/CIL/REL imipenem/cilastatin/relebactam, MITT modified intent-to-treat, PIP/TZP piperacillin/tazobactam.