Int J Antimicrob Agents. 2023 Apr 24:106830. doi: 10.1016/j.ijantimicag.2023.106830. Online ahead of print.
OBJECTIVE: This meta-analysis aimed at assessing the clinical efficacy and safety of novel antibiotics for complicated urinary tract infections (cUTIs).
METHODS: Three electronic databases including Medline, Embase, and Cochrane library were searched from inception till October 20, 2022 to identify randomized controlled trials (RCTs) investigating the efficacy and safety of novel antibiotics (including novel β-lactam/β-lactamase inhibitor combinations, aminoglycoside, fluoroquinolone, 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: A total of eleven RCTs demonstrated a higher CCR (83.6% vs 80.3%; odds ratio [OR]=1.37; 95%CI:1.08-1.74; p=0.01, I2 = 35%, 11 RCTs, 3514 participants) and microbiological eradication rate (77.7% vs 67.2%; OR=1.79; 95%CI:1.46-2.20; p<0.00001, 11 RCTs, 4347 participants) at TOC in the intervention group than those in the controls. There was no significant difference between the intervention and control groups in CCR at EOT (OR=0.96; p=0.81, I2=4%, nine RCTs, 3429 participants) and risk of treatment-emergent AE (OR=0.95; p=0.57, I2=51%; 11RCTs, 5790 participants). TSA showed robust evidence 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 ones for patients with cUTIs. However, as the pooled evidence relating to CCR remained inconclusive, further studies are required to address this issue.