FDA Approves Imipenem, Cilastatin, and Relebactam for cUTI, cIAI

The US Food and Drug Administration (FDA) has approved imipenem, cilastatin, and relebactam (Recarbrio) 1.25 grams for injection for treatment of adults with complicated urinary tract (cUTI) and complicated intra-abdominal (cIAI) bacterial infections where limited or no alternative options are available. 



The approval of the new drug application (NDA), which was submitted in February 2019 and received Priority Review designation, provides relief to patients who have limited options for the treatment of CUTI and cIAI caused by susceptible gram-negative microorganisms. 



“Recarbrio provides an important addition to our toolkit in the ongoing fight against infections caused by certain Gram-negative pathogens,” said Keith Kaye, MD, professor of medicine and director of research for the division of infectious diseases, University of Michigan Heath System, and a principal investigator in the clinical program. “Recarbrio offers an additional treatment option for patients with cIAI and cUTI who have limited and, in some cases, no alternative therapeutic options.”



In a press release, Merck, which produces the novel treatment, cited the results of the RESTORE-IMI 1 trial as the basis of the FDA approval of imipenem, cilastatin, and relebactam. The multi center, randomized, double-blind, comparator-controlled trial examined imipenem, cilastatin, and relebactam versus colistin plus imipenem and clistatin (COL+IMI) in 47 patients with bacterial infections. 


The study’s primary endpoint was favorable overall response in the microbiological modified intent-to-treat population and secondary end points were favorable clinical response at 28 days, 28-day all-cause mortality, incidence of adverse events, and incidence of treatment emergent nephrotoxicitiy. Of the 47 participants, 31 of them met the primary endpoint of the study.




Upon analysis, investigators found that the favorable overall response of imipenem, cilastatin, and relebactam was comparable to the COL+IMI treatment group (71.4% versus 70%). Additionally, investigators noted favorable clinical response at day 28 was higher in the imipenem, cilastatin, and relebactam group (71.4%) compared to the COL+IMI group (40.4%).

Investigators noted that drug-related adverse events among patients in the imipenem, cilastatin, and relebactam was nearly half that of the COL+IMI group (16.1% versus 31.3%). Additionally, treatment-emergent nephrotoxicity was lower in the imipenem, cilastatin, and relebactam group (10% versus 56%).

Imipenem, cilastatin, and relebactam should only be used to treat or prevent infections that are proven or suspected to be caused by susceptible bacteria. Merck added they anticipate imipenem, cilastatin, and relebactam to be available later this year.

Imipenem, cilastatin, and relebactam’s approval for treatment of cUTI includes those caused by Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The approval for treatment of cIAI includes those caused by Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis and Pseudomonas aeruginosa.