Relebactam

Relebactam is an intravenously administered inhibitor of class A and C beta-lactamases.

Multi-resistant, Gram-negative pathogens are becoming increasingly important. Carbapenemase-forming enterobacteria, which are now resistant to numerous antibiotics, are particularly problematic. In preclinical studies, it showed antibacterial activity in combination with imipenem/cilastatin against a broad spectrum of Gram-negative and betalactam-resistant pathogens. As a result, Relebactam was classified as aQualified Infectious Disease Product (QIDP) in July 2019 and granted fast track status for the treatment of nosocomial pneumonia, ventilator-associated pneumonia, complicated intra-abdominal infections and complicated urinary tract infections.

In the US, Relebactam is approved since 2019 in fixed combination with Imipenem 500 mg, Cilastatin 500 mg, Relebactam 250 mg. Later also in the EU (Recarbrio). Recarbrio is indicated for the: treatment of hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) in adults. Treatment of bacteremia for which there is or is suspected to be an association with HAP or VAP in adults. Treatment of infections with aerobic Gram-negative pathogens in adults with limited treatment options.

Recarbrio may be used in adults for whom there are limited or no treatment options and whose infection is caused by the following pathogens: 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 or Pseudomonas aeruginosa.

The most common side effects were nausea, diarrhea, headache, fever and elevated liver enzymes.

Rarely, Clostridioides difficile-associated diarrhea (CDAD) occurs with Recarbrio. The severity of CDAD can range from mild diarrhea to fatal colitis. CDAD should be considered in all patients if they experience diarrhea during or after Recarbrio use. A careful history is required, as an occurrence of CDAD has been reported more than two months after antibiotic use. In case of suspected or confirmed CDAD, discontinuation of treatment with Recarbrio and use of specific treatment against C. difficile should be considered.

The approval is based on the Phase II studies NCT01505634 and NCT01506271, which respectively enrolled subjects with complicated urinary tract infections and complicated intra-abdominal infections.

1. Campanella TA et al. (2020) Clinical Review and Critical Evaluation of Imipenem-Relebactam: Evidence to Date. Infect Drug Resist 13:4297-4308.
2. Smith JR et al.(2020) Imipenem-cilastatin-elebactam: A Novel β-lactam-β-lactamase Inhibitor Combination for the Treatment of Multidrug-Resistant Gram-Negative Infections. Pharmacotherapy 40:343-356.
3. Yahav D et al (2020) New β-lactam-β-lactamase inhibitor combinations. Clin Microbiol Rev 34:e00115-20.