FDA OKs Antibiotic for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia

June 8, 2020

Officials with the FDA have approved imipenem, cilastatin, and relebactam (Recarbrio, Merck) for the treatment of adults with hospital-acquired and ventilator-associated bacterial pneumonia. 

Officials with the FDA have approved imipenem, cilastatin, and relebactam (Recarbrio, Merck) for the treatment of adults with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP), according to a press release. 

Imipenem, cilastatin, and relebactam is indicated for patients with HABP/VABP caused by the following susceptible Gram-negative microorganisms: Acinetobacter calcoaceticus-baumanniicomplex, Enterobacter cloacaeEscherichia coliHaemophilus influenzaeKlebsiella aerogenesKlebsiella oxytocaKlebsiella pneumoniaePsueodomonas aeruginosa, and Serratia marcescens

The approval of this supplemental New Drug Application was based on data from the phase 3 multinational randomized double-blind noninferiority RESTORE-IMI 2 trial, which evaluated the safety and efficacy of imipenem 500 mg, cilastatin 500 mg, and relebactam 250 mg compared with piperacillin 4000 mg and tazobactam 500 mg (PIP/TAZ) in adults with HABP/VABP. The study included 535 hospitalized adults with HABP/VABP who were randomized 1:1 to receive a dose of imipenem, cilastatin, and relebactam or PIP/TAZ, each given intravenously every 6 hours for 7 to 14 days. 

Overall, imipenem, cilastatin, and relebactam demonstrated noninferiority to PIP/TAZ. For patients treated with imipenem, cilastatin, and relebactam, 28-day all-cause mortality was 15.9% and 21.3% in those treated with PIP/TAZ, for a treatment difference of -5.2% (95% CI: -11.9, 1.2). Clinical response at early follow-up was 61% for imipenem, cilastatin, and relebactam and 55.8% for PIP/TAZ group, for a treatment difference of 5% (95% CI: -3.2, 13.2), according to the data. 

Serious adverse effects (AEs) occurred in 27% of patients receiving imipenem, cilastatin, and relebactam and 32% of patients receiving PIP/TAZ. The most frequently reported AEs occurring in 4% or greater of patients with imipenem, cilastatin, and relebactam were increased aspartate aminotransferase (11.7%), anemia (10.5%), increased alanine aminotransferase (9.8%), diarrhea (7.9%), hypokalemia (7.9%), hypotranemia (6.4%), constipation (4.1%), pyrexia (4.1%), and rash (4.1%).

Imipenem, cilastatin, and relebactam is also indicated in adults who have limited or no alternative treatment options for complicated urinary tract infections, including pyelonephritis, and complicated intraabdominal infections caused by susceptible Gram-negative bacteria. 

“Hospital-acquired infections continue to be a significant cause of illness and death despite advances in our understanding of the contributing factors and prevention of these diseases,” principal study investigator Keith Kaye, MD, MPH, professor of medicine and director of research for the division of infectious diseases, University of Michigan Health System, said in a statement. “Because these infections are often caused by difficult to treat Gram-negative organisms, new therapeutic options such as Recarbrio are urgently needed for patients.”

 

 

References:

1. FDA Approves Merck's RECARBRIO (imipenem, cilastatin, and relebactam) for the Treatment of Adults with Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP). News Release. Merck; June 5, 2020. Accessed June 8, 2020. https://www.mrknewsroom.com/newsroom/news-releases/news-details/2020/FDA-Approves-Mercks-RECARBRIO-imipenem-cilastatin-and-relebactam-for-the-Treatment-of-Adults-with-Hospital-Acquired-and-Ventilator-Associated-Bacterial-Pneumonia-HABPVABP/default.aspx.