Nitroxoline: A "Re-Emerging" Antibacterial Agent in the Prevention of Recurrent Urinary Tract Infection Based on Updated Worldwide Guidelines

Abstract

Introduction. Urinary tract infections (UTIs) represent a critical global healthcare challenge, impacting over 404 million individuals annually. Escalating antimicrobial resistance among primary uropathogens, particularly to fluoroquinolones and broad-spectrum beta-lactams, has driven a critical paradigm shift toward antibiotic-sparing agents. Nitroxoline (5-nitro-8-hydroxyquinoline), an oral uroantiseptic, has re-emerged as a promising therapeutic alternative.

Material and methods. This narrative review synthesizes current clinical and microbiological evidence regarding nitroxoline's mechanism of action, pharmacokinetics, safety profile, and resistance rates. Furthermore, it evaluates the drug's therapeutic positioning across updated international clinical guidelines published up to May 2026.

Results. Nitroxoline exhibits broad-spectrum activity against Enterobacterales (including ESBL strains), urogenital mycoplasmas, and Candida species. Its antimicrobial effect is driven by the chelation of essential divalent metallic cations, which inhibits bacterial RNA polymerase, reduces biofilm synthesis, inhibits metallo-beta-lactamases, and impairs mucosal adhesion. Oral nitroxoline achieves rapid, high urinary concentrations with low disruption to native intestinal microflora. Clinical data demonstrate high tolerability (~96%) and a minimal discontinuation rate (~1.3%). Major European consensus guidelines (EAU, AWMF, SSGO) recommend nitroxoline as a first-line oral agent for acute localized cystitis and prophylaxis where available. Guidelines in non-registered regions omit the drug solely due to regional market unavailability.

Conclusions. Nitroxoline is a potent, safe, and antibiotic-sparing uroantiseptic that aligns with global antimicrobial stewardship principles. Future efforts should focus on expanding clinical trials and clarifying its pharmacokinetics in renal impairment to fully utilize its therapeutic potential against resistant uropathogens.