Urinary Tract Infections (2/4): Causes, Pathogens and Risk Factors

Urinary tract infection (1/4): definition and epidemiology
Urinary tract infection (2/4): causes and risk factors
Urinary tract infection (3/4): Diagnostic Work-Up
Urinary tract infection (4/4): 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 colonization:

Urinary tract infections are most often caused by ascending colonization, possible are hematogenous or lymphatic colonization and invasion of pathogens from neighboring organs.

Ascending infection:

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

Hematogenous infection:

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

Lymphatic spread of urinary tract infection:

Lymphatic spread of UTI are rare and unsecured. There are speculations about the lymphatic spread of rectal bacteria to prostate, bladder, and internal female sex organs.

Direct spread from adjacent organs:

Urinary tract infections may be causes by direct spread of abscess or fistula formation (e.g. abscess after PID, vesicovaginal fistula, vesicosigmoidal fistula).

Pathogens in Urinary Tract Infections:

Pathogens of uncomplicated urinary tract infections are most common 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.
Pathogens	%
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

Further 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 UTIs are caused by E. coli (80% of ambulatory patients). Uropathogenic E. coli (UPEC) tend to adhere more tightly to the urothelium and vaginal epithelium. The increased adherence is mediated by fimbriae or pili. The subdivision of virulence factors of E. coli involves the ability to agglutinate animal erythrocytes and on the possibility to inhibit the agglutination with sugar: type 1 pili (mannose-sensitive hemagglutnation = MSHA) and type 2 pili (mannose-resistant hemagglutination = MRHA).

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.

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 3 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, ileum conduit and neurogenic bladder disorders.
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 dilation 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

Urinary tract infection

Index

Diagnosis of UTI

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

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References

Deutsche Gesellschaft für Urologie, S3-guideline for urinary tract infection: Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten
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Deutsche Version: Ursachen einer Harnwegsinfektion

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