This systematic review was conducted to compare the efficacy of non-carbapenem β-lactam/β-lactamase inhibitors (BLBLIs) versus carbapenems for the treatment of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). A comprehensive search of the Cochrane Library, PubMed and Embase was conducted from January 1979 to December 2020. Clinical success, microbiological success, clinical and microbiological success, and mortality were assessed as efficacy outcomes. Heterogeneity was assessed using the I statistic, and a fixed-effects or random-effects model was applied for estimation of the risk ratio (RR). A total of 1612 patients from three randomised clinical trials (RCTs) and seven cohort studies were included in the meta-analysis. There was no statistically significant difference between BLBLIs and carbapenems in clinical success (RR = 0.99; P = 0.71), clinical and microbiological success (RR = 0.97; P = 0.46) and mortality (RR = 0.63; P = 0.22). A slightly higher rate of microbiological success was observed in BLBLI group (RR = 1.06; P = 0.01), which was mainly attributed to the efficacy of ceftazidime/avibactam based on a single RCT. BLBLIs were not inferior to carbapenems, with higher microbiological success, indicating an effective alternative non-carbapenem option for the treatment of UTIs caused by ESBL-PE. More high-quality and large-scale RCTs are required to further validate these findings. [Trial registration: PROSPERO ID: CRD42021233706].
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