Imipenem-Cilastatin-Relebactam: A Novel β-Lactam-β-Lactamase Inhibitor Combination for the Treatment of Multidrug-Resistant Gram-Negative Infections

Link to article at PubMed

Smith JR, et al. Pharmacotherapy 2020.


Imipenem-cilastatin-relebactam (IMI-REL) is a novel β-lactam-β-lactamase inhibitor combination recently approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intraabdominal infections (cIAIs). Relebactam is a β-lactamase inhibitor with the ability to inhibit a broad spectrum of β-lactamases such as class A and class C β-lactamases, including carbapenemases. The addition of relebactam to imipenem restores imipenem activity against several imipenem-resistant bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. Clinical data demonstrate that IMI-REL is well tolerated and effective in the treatment of cUTIs and cIAIs due to imipenem-resistant bacteria. In a phase III trial comparing IMI-REL with imipenem plus colistin, favorable clinical response was achieved in 71% and 70% of patients, respectively. Available clinical and pharmacokinetic data support the approved dosage of a 30-minute infusion of imipenem 500 mg-cilastatin 500 mg-relebactam 250 mg every 6 hours, along with dosage adjustments based on renal function. In this review, we describe the chemistry, mechanism of action, spectrum of activity, pharmacokinetics and pharmacodynamics, and clinical efficacy, and safety and tolerability of this new agent. The approval of IMI-REL represents another important step in the ongoing fight against multidrug-resistant gram-negative pathogens.

PMID:32060929 | DOI:10.1002/phar.2378

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