Urinary tract infections: current and emerging management strategies

Abstract

Acute cystitis is one of the most commonly encountered bacterial infections and is responsible for substantial morbidity and high medical costs in the United States and across the globe. Though generally considered to be self-limiting and easily treated with antibiotics, urinary tract infections (UTIs) are often incompletely resolved by antibiotic therapy and frequently recur. This is in part due to the ability of uropathogenic bacteria to invade, replicate, and persist within host epithelial cells. The biological complexity of these infections combined with a dramatic rise in antibiotic-resistant pathogens highlight the need for alternative therapies. In this review we examine current management strategies for UTIs, as well as emerging treatments, including novel compounds that block bacterial interactions with the urothelium and vaccines focused on preventing both acute and recurrent infections.

Keywords: UPEC; antibiotic resistance; cystitis; recurrent UTI; vaccine.

Figure 1.

Events that promote the establishment and recurrence of urinary tract infection (UTI). (1) During a UTI, uropathogenic Escherichia coli (UPEC; green) can replicate within the lumen of the bladder or (2) attach to and invade bladder epithelial cells. (3) Following invasion, UPEC is either shuttled back out to the lumen or trafficked into late endosome-like compartments. (4) Disruption of these compartments and subsequent entry of UPEC into the host cytosol allows for rapid intracellular bacterial growth and the development of intracellular bacterial community. During these events, UPEC can acquire alternate morphologies, including the formation of long, filamentous cells that are resistant to host defenses such as neutrophils. (5) Infection can trigger the exfoliation of bladder cells, a process that aids in the elimination of adherent and internalized bacteria. The efflux of UPEC from host bladder cells, including those undergoing exfoliation, facilitates pathogen dissemination within and between hosts. (6) UPEC that remains bound within late endosome-like compartments in the urothelium can establish long-lived intracellular quiescent reservoirs that are often enmeshed within actin filaments (red) and extremely difficult to eradicate with antibiotic treatments. The resurgence of UPEC from these reservoirs can initiate recrudescent infections. Abbreviation: IBC, intracellular bacterial community.