Review
Pathogenesis of urinary tract infections with normal female anatomy

https://doi.org/10.1016/S1473-3099(04)01147-8Get rights and content

Summary

Recurrent urinary tract infections (UTIs) are common among girls and young women who are healthy and have anatomically normal urinary tracts. These infections are a main source of morbidity and health-care costs in this population. The interaction between specific infecting bacteria and urinary tract epithelium characteristics underlies the pathogenesis of this disease. Several pathogen-related factors predispose people to recurrent UTI, including periurethral bacterial colonisation and Escherichia coli virulence. Host behavioural risk factors include voiding dysfunction, high intercourse frequency, and oral contraceptive and spermicide use. The role of vesicoureteral reflux in recurrent childhood UTI is probably overestimated in the medical literature and is important only in a small group of children with high-grade reflux. Family pedigree analysis suggests a familial genetic predisposition for UTI among young females. Animal models show the multigenic nature of recurrent UTI. Putative candidate genes for the disease include ABH blood groups, interleukin −8 receptor (CXCR1), the human leucocyte antigen locus, toll-like receptors, tumour necrosis factor, and Tamm-Horsfall protein.

Section snippets

Pathogenesis

Most uncomplicated UTIs in women cannot be explained by underlying functional or anatomic abnormalities of the urinary tract, but instead seem to result from the interaction between the infecting Escherichia coli strains and the urinary tract epithelium (figure). Colonisation of the vaginal introitus with E coli seems to be one of the critical initial steps in the pathogenesis of both acute and recurrent UTI. In healthy individuals, most uropathogens originate in the rectal flora and enter the

Bacterial factors

In a prospective, community-based study of 131 episodes of recurrent UTI during 1 year, E coli was the cause of 78% of the recurrent episodes. Uropathogenic E coli have several virulence factors that increase their ability to colonise and persist in the urogenital tract.16 Binding to the urothelial surface is one factor that prevents bacterial washout by micturition and initiates bacterial invasion. This binding is mediated by the FimH adhesion located at the tip of the bacterial type 1

Voiding dysfunction

Voiding dysfunction is defined as a voiding pattern that is abnormal for age. The symptoms of voiding dysfunction include urinary urgency, frequency, and incontinence as well as infrequent voiding. Voiding disorders are common in paediatric patients who have neither neurological nor anatomic abnormalities of the urinary tract, and usually result from detrussor muscle instability. Children with detrussor instability who use various posturing manoeuvres to avoid urinary incontinence have a

Behavioural risk factors

The genital flora surrounding the urethral orifice have a strong resistance to infection from uropathogens. In normal women who never experience UTI, the main introital, vaginal, and urethral microbial flora consists of lactobacilli and staphylococci.12 Previous antibiotic use profoundly disturbs the normal vaginal microflora, reduces its adherence to vaginal epithelial cells in vivo and promotes a persistent vaginal E coli colonisation.33 Vaginal fluid from women with recurrent UTIs more

Search strategy and selection criteria

Data for this review were identified by searches of Medline and references from relevant articles; several articles were identified through searches of the extensive files of the authors. Search terms were included in the Medical Subject Heading (MeSH) system and included “urinary tract infections” and “recurrence”. The search was then limited to clinical studies including “female” and “human”, and excluding “pregnancy” and “post menopause”. Only English language papers were reviewed.

References (74)

  • SJ Hultgren et al.

    Pilus and nonpilus bacterial adhesins: assembly and function in cell recognition

    Cell

    (1993)
  • B Wullt

    The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract

    Int J Antimicrob Agents

    (2003)
  • TS Elliott et al.

    Bacteriology and ultrastructure of the bladder in patients with urinary tract infections

    J Infect

    (1985)
  • R Beetz et al.

    Long-term followup of 158 young adults surgically treated for vesicoureteral reflux in childhood: the ongoing risk of urinary tract infections

    J Urol

    (2002)
  • TP Bukowski et al.

    Urinary tract infections and pregnancy in women who underwent antireflux surgery in childhood

    J Urol

    (1998)
  • JT Mansfield et al.

    Complications of pregnancy in women after childhood reimplantation for vesicoureteral reflux: an update with 25 years of followup

    J Urol

    (1995)
  • CM Stauffer et al.

    Family history and behavioral abnormalities in girls with recurrent urinary tract infections: a controlled study

    J Urol

    (2004)
  • S Hansson et al.

    The natural history of bacteriuria in childhood

    Infect Dis Clin North Am

    (1997)
  • WJ Hopkins et al.

    Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection

    Vaccine

    (1999)
  • KM Kroeger et al.

    The -308 tumor necrosis factor-alpha promoter polymorphism affects transcription

    Mol Immunol

    (1997)
  • JM Bates et al.

    Tamm-Horsfall protein knockout mice are more prone to urinary tract infection

    Kidney Int

    (2004)
  • J Pak et al.

    Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E coli from binding to uroplakin Ia and Ib receptors

    J Biol Chem

    (2001)
  • F Serafini-Cessi et al.

    Tamm-Horsfall glycoprotein: biology and clinical relevance

    Am J Kidney Dis

    (2003)
  • H Reinhart et al.

    Urinary excretion of Tamm-Horsfall protein in women with recurrent urinary tract infections

    J Urol

    (1990)
  • DT Uehling et al.

    Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections

    J Urol

    (2003)
  • A Nayir et al.

    The effects of vaccination with inactivated uropathogenic bacteria in recurrent urinary tract infections of children

    Vaccine

    (1995)
  • X Li et al.

    Vaccines for Proteus mirabilis in urinary tract infection

    Int J Antimicrob Agents

    (2002)
  • A Stapleton

    Novel approaches to prevention of urinary tract infections

    Infect Dis Clin North Am

    (2003)
  • TM Hooton et al.

    A prospective study of risk factors for symptomatic urinary tract infection in young women

    N Engl J Med

    (1996)
  • WE Stamm et al.

    Management of urinary tract infections in adults

    N Engl J Med

    (1993)
  • JC Craig

    Urinary tract infection: new prospectives on a common disease

    Curr Opin Infect Dis

    (2001)
  • M Nuutinen et al.

    Recurrence and follow-up after tract infection under the age of 1 year

    Pediatr Nephrol

    (2001)
  • N Le Saux et al.

    Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract infections in children: a systematic review

    CMAG

    (2000)
  • U Jodal et al.

    Management of children with unobstructed urinary tract infection

    Pediatr Nephrol

    (1987)
  • FK Bahrani-Mougeot et al.

    Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli virulence determinants in the murine urinary tract

    Mol Microbiol

    (2002)
  • ME Jantunen et al.

    Recurrent urinary tract infections in infancy: relapses or reinfections?

    J Infect Dis

    (2002)
  • TA Russo et al.

    Chromosomal restriction fragment length polymorphism analysis of Escherichia coli strains causing recurrent urinary tract infections in young women

    J Infect Dis

    (1995)
  • Cited by (93)

    • Specific capture of Pseudomonas aeruginosa for rapid detection of antimicrobial resistance in urinary tract infections

      2023, Biosensors and Bioelectronics
      Citation Excerpt :

      Complicated UTIs are among the major causes of bacteremia and are related to a high mortality rate for critically ill patients (Chan and Yuen, 2015; To et al., 2013; Wagenlehner et al., 2008). Additionally, recurrent UTIs are common among young and healthy females, although they generally possess normal urinary tracts in the anatomical and physiological regards (Finer and Landau, 2004). Toward UTIs, particularly complicated UTIs, broad-spectrum antibiotics are empirically employed against uropathogenic Gram-negative bacteria (Chan and Yuen, 2015; Flores-Mireles et al., 2015).

    • Influence of gender on the performance of urine dipstick and automated urinalysis in the diagnosis of urinary tract infections at the emergency department

      2021, European Journal of Internal Medicine
      Citation Excerpt :

      Beside incidence, also differences in presentation and course of UTI exist between men and women. This is due to a variety of factors, like (pelvic) anatomic differences, voiding issues, and vaginal mucosa colonization [4-8]. In addition, differences in causing uropathogens exist between men and women [9].

    • The aberrant urethral meatus as a possible aetiological factor of recurrent post-coital urinary infections in young women

      2018, Medical Hypotheses
      Citation Excerpt :

      Unfortunately, scarcely any studies mention the need for thorough physical examination and anatomical evaluation; the recent recommendations of the American Academy of Family Physicians do not include regular physical examination, even in cases or recurrent UTI episodes, as it has “limited utility and is not universally recommended” [26]. Other reviews on rUTIs state that the possibility of an underlying anatomical anomaly is very low [1,16]. However it is obscure whether the urethra – vagina distance - which has never received any attention- would be considered and evaluated as an “anatomical anomaly” by most physicians.

    View all citing articles on Scopus
    View full text