Recurrent urinary tract infections in healthy and nonpregnant women

Abstract

Recurrent urinary tract infections (RUTI) are prevalent and pose significant clinical challenges. Although the term RUTI has long been vaguely defined, a consensus definition has emerged in recent years. The exact etiology behind RUTI remains under debate, with valid arguments for both ascending reinfections as well as persistent infection inside the bladder. These persistent infections exist in the form of quiescent intracellular reservoirs in the mouse model and may represent a novel concept to explain UTI recurrence in humans. Manageable risk factors such as behavioral patterns alongside nonmanageable risk factors including genetic susceptibility are growing fields of investigation. Acute UTI have been studied through two model bacterial strains: Escherichia coli UTI89 and CFT073. However, the clinical relevance to RUTI of these two strains has not been firmly established. Current treatment strategies for RUTI are limited and remain dominated by antibiotic usage despite variable efficacy. The majority of studies in humans have focused on younger groups of women with little information available about the postmenopausal population despite a heightened risk of RUTI in this age group.

Keywords: intracellular bacterial communities; postmenopausal women; quiescent intracellular reservoir; recurrent urinary tract infections; reinfection; risk factors for urinary tract infections.

Fig. 1

Uropathogenic Escherichia coli model for acute cystitis, chronic cystitis, and quiescent intracellular reservoir formation: intracellular bacterial community (IBC) formation starts when bacteria attach onto the apical transitional epithelium of the bladder via type 1 pili. These bacteria are then enveloped and invade the epithelium – replicating and forming IBCs. As a host response to infection, the urothelium typically exfoliates, resulting in IBC liberation and IBC recreation in a clonal fashion. IBCs may also progress to quiescent intracellular reservoirs, which are not metabolically active and do not produce a measurable inflammatory response. Note. From “Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection,” by T.J. Hannan, M. Totsika, K.J. Mansfield, K.H. Moore, M.A. Schembri, and S.J. Hultgren, 2012, FEMS Microbiol Rev, 3, p. 616–48. Copyright 2012, Nature Publishing Group. Reprinted with permission.

Fig. 2

Ascending reinfection. Uropathogens originate from the rectal flora and colonize the periurethral area leading to ascension through the urethra into the bladder. Note. From “Pathogenic Escherichia coli” by J.B. Kaper, J.P. Nataro, and H.L. Mobley, 2004. Nat Rev Microbiol, 2, p. 123–40. Copyright 2004. Nature Publishing Group. Reprinted with permission.