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

Kuo-Chuan Hung; Wen-Wen Tsai; Chin-Wei Hsu; Chih-Cheng Lai; Hung-Jen Tang; I-Wen Chen

doi:10.1016/j.ijantimicag.2023.106830

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

Int J Antimicrob Agents. 2023 Jul;62(1):106830. doi: 10.1016/j.ijantimicag.2023.106830. Epub 2023 Apr 24.

Authors

Kuo-Chuan Hung¹, Wen-Wen Tsai², Chin-Wei Hsu³, Chih-Cheng Lai⁴, Hung-Jen Tang⁵, I-Wen Chen⁶

Affiliations

¹ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Anaesthesiology, Chi Mei Medical Centre, Tainan City, Taiwan.
² Department of Education, Chi Mei Medical Centre, Tainan City, Taiwan.
³ Department of Pharmacy, Chi Mei Medical Centre, Tainan, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan.
⁵ Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan.
⁶ Department of Anaesthesiology, Chi Mei Medical Centre, Liouying, Tainan City, Taiwan. Electronic address: mavising@gmail.com.

PMID: 37100354
DOI: 10.1016/j.ijantimicag.2023.106830

Abstract

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 β-lactam/β-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones 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% confidence interval (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 compared with the control group. At EOT, there was no significant difference in CCR (OR 0.96, P=0.81, I²=4%, nine RCTs, 3429 participants) or risk of treatment-emergent AEs (OR 0.95, P=0.57, I²=51%, 11 RCTs, 5790 participants) between the intervention and control groups. 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 antibiotics for patients with cUTIs. However, as the pooled evidence relating to CCR remained inconclusive, further studies are required to address this issue.

Keywords: Cefepime/enmetazobactam; Cefiderocol; Ceftazidime/avibactam; Ceftolozane/tazobactam; Complicated urinary tract infection; Finafloxacin; Imipenem/cilastatin plus relebactam; Meropenem/vaborbactam; Plazomicin.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Anti-Bacterial Agents* / adverse effects
Humans
Randomized Controlled Trials as Topic
Treatment Outcome
Urinary Tract Infections* / drug therapy
Urinary Tract Infections* / microbiology
beta-Lactamase Inhibitors / therapeutic use

Substances

Anti-Bacterial Agents
beta-Lactamase Inhibitors