AUTHOR=Yang Qingxin , Yang Yanqiu , He Rong , Yu Bin , Zhong Yueling , Lin Fei 

TITLE=Efficacy and safety of novel carbapenem-β-lactamase inhibitor combinations: imipenem-cilastatin/relebactam results from randomized controlled trials

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1304369

DOI=10.3389/fmed.2023.1304369

ISSN=2296-858X

ABSTRACT=Background: Gram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors.The objective of this study was to collect information on the efficacy and safety of novel β-lactamase inhibitor combinations such as imipenemcilastatin/relebactam (IMI/REL).In order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel β-lactamase inhibitor combinations with existing comparator therapies.Results: Four studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits (DCIV, RR = 1.00 [0.88, 1.12]), early follow-up visits (EFU, RR = 1.00 [0.89, 1.14], late follow-up visits (LFU, RR = 1.00 [0.88, 1.13]). Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV (RR = 0.99 [0.89, 1.11]), EFU (RR = 1.01 [0.95, 1.07]), and LFU visits (RR = 1.00 [0.94, 1.07]). In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators.The clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators.Based on these findings, IMI/REL can be considered as a viable alternative treatment option.