Preclinical Evaluation of Nitroxide-Functionalised Ciprofloxacin as a Novel Antibiofilm Drug Hybrid for Urinary Tract Infections
Abstract
Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates and can involve biofilm formation on patient catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Many antibiofilm agents alone do not have bactericidal activity; therefore, linking them to antibiotics is a promising antibiofilm strategy. However, many of these hybrid agents have not been tested in relevant preclinical settings, limiting their potential for clinical translation. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against uropathogenic Escherichia coli (UPEC) strain UTI89 in vitro, as a potential UTI therapeutic using multiple preclinical models that reflect various aspects of UTI pathogenesis. We report improved in vitro activity over the parent drug ciprofloxacin against mature UTI89 biofilms formed inside polyethylene catheters. In bladder cell monolayers infected with UTI89, treatment with CDN11 afforded significant reduction in bacterial titers, including intracellular UPEC. Infected mouse bladders containing biofilm-like intracellular reservoirs of UPEC UTI89 showed decreased bacterial loads after ex vivo bladder treatment with CDN11. Activity for CDN11 was reported across different models of UTI, showcasing nitroxide–antibiotic hybridization as a promising antibiofilm approach. The pipeline we described here could be readily used in testing…
Read the paper
Related studies
- Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes
- Mutation supply and relative fitness shape the genotypes of ciprofloxacin-resistant Escherichia coli
- Genomic Survey of E. coli From the Bladders of Women With and Without Lower Urinary Tract Symptoms
- Characterization of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017–18
- Fitness cost constrains the spectrum of marR mutations in ciprofloxacin-resistant Escherichia coli
- Emerging evidence-based innovative approaches to control catheter-associated urinary tract infection: a review
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.