Clinical efficacy and safety of novel antibiotics for complicated urinary tract infection: A systematic review and meta-analysis of randomized controlled trials

Objective: To assess the clinical efficacy and safety of novel antibiotics for complicated urinary tract infections (cUTIs).Methods: Three electronic databases (Medline, Embase and the Cochrane Library) were searched from inception until 20 October 2022 to identify randomized controlled trials (RCTs) investigating the efficacy and safety of novel antibiotics (novel & beta;-lactam/ & beta;-lactamase inhibitor combinations, aminoglycosides, flu-oroquinolones and cefiderocol) against cUTIs. The primary outcome was the clinical cure rate (CCR) at test of cure (TOC), while secondary outcomes included CCR at end of treatment (EOT), microbiological eradication rate, and the risk of adverse events (AEs). Trial sequential analysis (TSA) was used to examine the evidence.Results: In total, 11 RCTs demonstrated a higher CCR [83.6% vs 80.3%, odds ratio (OR) 1.37, 95% confi-dence interval (CI) 1.08-1.74, P = 0.01, I 2 = 35%, 11 RCTs, 3514 participants] and microbiological eradication rate (77.7% vs 67.2%, OR 1.79, 95% CI 1.46-2.20, P < 0.0 0 0 01, 11 RCTs, 4347 participants) at TOC in the inter-vention group compared with the control group. At EOT, there was no significant difference in CCR (OR 0.96, P = 0.81, I 2 = 4%, nine RCTs, 3429 participants) or risk of treatment-emergent AEs (OR 0.95, P = 0.57, I 2 = 51% , 11 RCTs, 5790 participants) between the intervention and control groups. TSA showed robust ev-idence regarding microbiological eradication rate and treatment-emergent AEs, while the CCR at TOC and EOT remained inconclusive.Conclusions: While showing similar safety, the investigated novel antibiotics may be more effective than the conventional antibiotics for patients with cUTIs. However, as the pooled evidence relating to CCR remained inconclusive, further studies are required to address this issue.