Carbapenem-sparing beta-lactam/beta-lactamase inhibitors versus carbapenems for bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a systematic review and meta-analysis

Objectives: Bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Enter-obacteriaceae (ESBL-PE) have become a worldwide public health threat, and beta-lactam/beta-lactamase inhibitor combinations (BLBLIs) are considered as one reliable carbapenem-sparing antibiotic. However, it is still controversial whether BLBLIs are truly noninferior to carbapenems. Therefore, we conducted this meta-analysis to compare the efficacy of BLBLIs with carbapenems for ESBL-PE BSIs.Methods: A systematic search of PubMed, Cochrane Library, and Embase was conducted until December 2021 to enroll studies comparing BLBLIs with carbapenems for ESBL-PE BSIs. A subgroup analysis was performed based on the choice of therapy (empirical, definitive, and mixed therapy). The protocol was registered in the International Prospective Register of Systematic Reviews (#CRD42022316011).Results: A total of 2786 patients from one randomized clinical trial and 25 cohorts were included. There was no statistically significant difference between BLBLIs and carbapenems groups in therapeutical re-sponse (odds ratio [OR] = 1.19, P = 0.45) and mortality (OR = 1.06, P = 0.68). Furthermore, although the statistical difference was also not found in the subgroup analysis, BLBLIs performed better in defini-tive therapy than empirical therapy than carbapenems, with a numerically higher therapeutical response (OR = 1.42 vs 0.89) and a mildly lower mortality (OR = 0.85 vs 1.14).Conclusion: BLBLIs were noninferior to carbapenems for ESBL-PE BSIs, especially in definitive therapy. BLBLIs may be a valid alternative to spare the use of carbapenems.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This meta-analysis found that beta-lactam/beta-lactamase inhibitor combinations (BLBLIs) were noninferior to carbapenems for bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), especially in definitive therapy. BLBLIs may be a valid alternative to spare the use of carbapenems.