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Urinary Tract Infections: Causes, Pathogens, and Risk Factors

• Urinary tract infection: definition and epidemiology
• Urinary tract infection: causes and risk factors
• Urinary tract infection: Diagnostic Workup
• Urinary tract infection: prevention and antibiotic treatment

Review literature: (Krieger, 2002) (Nickel, 2005a) (Nickel, 2005b) (Sussman and Gally, 1999) (Wagenlehner and Naber, 2006) (DGU 2009, S3-guideline for UTI).

Etiology and Pathogenesis of Urinary Tract Infections

Mechanisms of Infections:

Bacteria can invade the urinary tract by ascending from the urethra, hematogenous spread, lymphatic spread and invasion via the neighboring organs.

Ascending infection:

Ascending infections are the most common cause of urinary tract infections. Because the female urethra is short and intestinal bacteria tend to colonize the perineum and vulva, women are more prone to UTIs than men.

Hematogenous infection:

Hematogenous-caused urinary tract infections are rare: urogenital tuberculosis, renal abscess, perinephric abscess, or epididymitis.

Lymphatic spread of urinary tract infection:

Lymphatic causes of UTI are rare and speculative; bacteria may spread to the prostate, bladder, and female internal genital organs in case of severe bowel inflammation.

Direct spread from adjacent organs:

Urinary tract infections may be causes by invasion from neighboring organs: through intraperitoneal abscess, pelvic inflammatory disease, bowel fistula (Crohn disease, diverticulitis, cancer), vesicovaginal fistula.

Pathogens in Urinary Tract Infections:

The most common bacteria of uncomplicated urinary tract infections are E. coli (80%), followed by Proteus mirabilis, Staphylococcus saprophyticus, and Klebsiella pneumoniae [Table pathogen spectrum of bacterial cystitis].

Other pathogens of urinary tract infections:

• Anaerobic Gram-positive pathogens: Peptococcus and Peptostreptococcus
• Neisseria gonorrhoeae
• Mycobacterium tuberculosis
• Fungi, most commonly Candida species (total 5% of UTI), and Aspergillus.
• Parasites: Schistosoma haematobium

Bacterial Virulence Factors in Urinary Tract Infections:

Most UTI are caused by E. coli (80% of outpatients). Uropathogenic E. coli (UPEC) adhere easily to the urothelium and vaginal epithelium. The increased adherence is mediated by fimbriae or pili. The classification is made regarding the ability to agglutinate animal erythrocytes and the sugars which inhibit this agglutination.

Most UTIs are caused by E. coli with MSHA or MRHA pili. The MSHA properties are responsible for binding to the urothelium, the MRHA property allows invasive infection. MSHA properties alone are not sufficient for urinary tract infection. Further bacterial virulence factors of E. coli are hemolysins (detroy urothelium cells), the formation of intracellular bacterial communities and biofilm production.

Type 1 pili:

Mannose-sensitive hemagglutination = MSHA. These bacteria can adhere to specific oligosaccharides of the urothelium.

Type 2 or P pili:

Mannose-resistant hemagglutination = MRHA. These bacteria can adhere to oligosaccharides on glycolipids of the urothelium and of P blood group antigens. In addition to the affinity to P blood group antigens, type 2 pili enable adherence to the kidney, and “P” standing for pyelonephritis.

Biofilm:

Bacteria attached to surfaces change their biochemical programm due to a complex change in intra- and intercellular signaling. This results in forming bacterial colonies, which are protected by a self-produced extracellular polymeric matrix called biofilm. Bacteria in biofilm colonies are more resistant to antibiotics, several mechanisms are proposed: 1) limited antibiotic diffusion through the matrix; 2) the transmission of resistance genes within the community; 3) physiological changes (reduced metabolism and growth rates) and 4) the presence of metabolically inactive cells known as persisters or dormant bacterial cells (Wieser et al., 2011).

Intracellular bacterial communities:

Uropathogenic bacteria can invade into urothelial cells and form an intracellular bacterial community (IBC) comparable to microbiological biofilms. IBC protect bacteria from the immune system, are the cause of recurrent UTI and may cause symptoms, while standard urine culture does not indicate UTI (Wieser et al., 2011).

Molecular risk factors:

Depending on the risk factor, either the risk for bacteriuria, for cystitis and/or pyelonephritis is increased: HLA-A3, a low secretion of the Lewis blood group antigen via the urine, blood group antigen P1, expression of the globo-A epitope (AB0 blood group system) on epithelial cells, secretion of IgA via the vaginal mucus, defects of the TLR4 (toll-like receptor), low uirne concentration of antimicrobial peptides (Ambite et al., 2016).

Gender-Independent Risk Factors for Urinary Tract Infection:

• Postvoid residual urine in the bladder
• Bladder catheter: from the third day, the prevalence of bacteriuria rises 3–8% per day. After three weeks, almost every bladder with catheter is colonized by bacteria.
• Disturbed peristalsis of the ureter, e.g., pregnancy
• Subvesical obstruction
• Decreased renal blood flow
• Non-secretors: a low secretion of the blood group antigens via the urine predisposes to recurrent UTI.
• Foreign bodies in the urinary tract
• Anatomical abnormalities: e.g., vesicoureteral reflux, ureteropelvic junction obstruction, ureterocele or bladder diverticulum.
• Diabetes mellitus: 20–25fold risk of urinary tract infections
• Risk factors for fungal infection of the urinary tract (Vazquez and Sobel, 1999): Diabetes mellitus, urinary tract obstruction, immunosuppression, catheterization, antibiotic therapy, female sex, ileal conduit and neurogenic lower urinary tract dysfunction.
• Fecal incontinence
• Old age

Female Risk Factors for Urinary Tract Infections:

• Short urethra enables ascending urinary tract infections.
• Increased sexual activity, anal intercourse, use of a diaphragm and/or spermicides.
• Pregnancy (hormone-induced dilatation of the urinary tract, decreased uromodulin)
• Postmenopause: the decreased estrogen levels lead to atrophy of the vaginal mucous membranes, reduced colonization by lactobacilli, increased vaginal colonization with Enterobacteriaceae and anaerobes, which cause urinary tract infections.

Male Risk Factors for Urinary Tract Infection:

• Missing circumcision predisposis children with vesicoureteral reflux to recurrent urinary tract infections.
• Reduced secretion of zinc by the prostate
• Sex with an infected partner or anal intercourse
• Foreskin diseases: e.g., balanitis

References

Kass 2002 KASS, E. H.: Asymptomatic infections of the urinary tract. 1956.
In: J Urol
167 (2002), Nr. 2 Pt 2, S. 1016–9; discussion 1019–21

Krieger 2002 KRIEGER, J. N.: Urinary tract infections: what’s new?
In: J Urol
168 (2002), Nr. 6, S. 2351–8

Nickel 2005a NICKEL, J. C.: Management of urinary tract infections: historical perspective and current strategies: Part 1–Before antibiotics.
In: J Urol
173 (2005), Nr. 1, S. 21–6

Nickel 2005b NICKEL, J. C.: Management of urinary tract infections: historical perspective and current strategies: Part 2-Modern management.
In: J Urol
173 (2005), Nr. 1, S. 27–32

Sobel und Vazquez 1999 SOBEL, J. D. ; VAZQUEZ, J. A.: Fungal infections of the urinary tract.
In: World J Urol
17 (1999), Nr. 6, S. 410–4

Sussman und Gally 1999 SUSSMAN, M. ; GALLY, D. L.: The biology of cystitis: host and bacterial factors.
In: Annu Rev Med
50 (1999), S. 149–58

Wagenlehner und Naber 2006 WAGENLEHNER, F. M. ; NABER, K. G.: Treatment of bacterial urinary tract infections: presence and future.
In: Eur Urol
49 (2006), Nr. 2, S. 235–44

  Deutsche Version: Ursachen einer Harnwegsinfektion