Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection

Abstract

Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.

Keywords: recurrence; urinary bladder; urinary tract infections; women.

Figure 1

The invasive process of uropathogenic Escherichia coli into the uroepithelium.

Figure 2

Potential antivirulence intervention for uropathogenic Escherichia coli. Schematic diagram illustrating alternative treatment options, including prophylactic strategies, antiadhesive treatments, immunomodulation therapy, and potential vaccines, that target the virulence of uropathogenic Escherichia coli.