Dr. med. Dirk Manski

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Urinary Tract Infections: Causes, Pathogens, and Risk Factors

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].

Pathogen spectrum of acute uncomplicated cystitis in women in Germany, modified after the S3 guideline for urinary tract infections of the DGU.
Gram-negative pathogens:
Escherichia coli 77
Proteus mirabilis 5
Klebsiella pneumoniae 2-3
Enterobacter spp. 1
Citrobacter spp. 1
Other Enterobacteriaceae 2
Gram-positive bacteria
Staphylococcus saprophyticus 3
Staphylococcus aureus 2
Other staphylococci 4
Enterococcus spp. 3
Streptococcus spp. 1

Other pathogens of urinary tract infections:

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 ā€œPā€ standing for pyelonephritis.


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:

Female Risk Factors for Urinary Tract Infections:

Male Risk Factors for Urinary Tract Infection:

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


Deutsche Gesellschaft für Urologie, S3-guideline for urinary tract infection
Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten
AWMF, 2010, Register-Nr. 043/044

Bauer u.a. 2002 BAUER, H. W. ; RAHLFS, V. W. ; LAUENER, P. A. ; BLESSMANN, G. S.: Prevention of recurrent urinary tract infections with immuno-active E. coli fractions: a meta-analysis of five placebo-controlled double-blind studies.
In: Int J Antimicrob Agents
19 (2002), Nr. 6, S. 451–6

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