Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis

Abstract

Background Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). Materials and Methods We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P -value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I 2 statistic. Results The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

Cost-Effectiveness of Imipenem/Cilastatin/Relebactam Compared with Colistin in Treatment of Gram-Negative Infections Caused by Carbapenem-Non-Susceptible Organisms

“…The ratio of ICU and general ward use between death vs cured is based on the hospital resource utilization analysis from the ASPECT-NP trial [41], which is limited to only ventilated HABP/VABP patients resource costs, and AE management cost. For the drug treatment cost, the wholesale acquisition costs for IMI/REL ($6688/25 vials 500 mg/ 250 mg units), CMS ($336/12 vials 150 mg), and IMI ($816/25 vials, 500 mg/500 mg) were sourced from the 2020 RED BOOK online database [13] and combined with trial-observed treatment durations to compute total acquisition costs [18]. Drug administration costs were not included in the model base case, as it is assumed these costs are implicitly captured by resource use (hospitalization) costs.…”

“…Imipenem/cilastatin/relebactam (IMI/REL), a combination of a b-lactam antibiotic (imipenem/cilastatin) and a novel b-lactamase inhibitor (relebactam), provides a treatment alternative with a favorable efficacy and tolerability profile for patients with CNS GNIs [13]. The novel b-lactamase inhibitor (relebactam) restores the activity of imipenem against imipenem-resistant isolates such as KPC-producing Enterobacterales and/or against Pseudomonas aeruginosa isolates showing CNS due to porin loss in combination with AmpC expression [13].…”

New evidence in severe pneumonia: imipenem/ cilastatin/relebactam

“…IMI/REL is a new antibiotic combination, bactericidal by its binding inhibition to penicillin binding proteins (PBP1 and PBP2). Recently, it has been approved by the FDA for use in ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) in June 2020 [1][2][3]. tration and active tubular secretion.…”

Comments on the Published Meta-Analysis of Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections

“…I read with great interest a recently published meta-analysis of Sahara et al [ 1 ] entitled “Clinical and microbiologic efficacy and safety of imipenem/cilastatin/relebactam in complicated infections: a meta-analysis.” According to the article, the systematic search was performed by related keywords in international databases; Cochrane Central Registry of Clinical Trials, Embase, and PubMed. After selection based on inclusion and exclusion criteria, four randomized controlled trials articles were included in this meta-analysis.…”