Urinary Tract Infections - General

Author: FME Wagenlehner, MD, PhD,   KG Naber, MD, PhD

Epidemiology of Urinary Tract Infections

Urinary tract infections (UTIs) are among the most prevalent infectious diseases with a substantial financial burden on society. In the USA, UTIs are responsible for over 7 million physician visits annually, including more than 2 million visits for cystitis. Approximately 15% of all community-prescribed antibiotics in the USA are dispensed for UTI, at an estimated annual cost of over US $1 billion. Furthermore, the direct and indirect costs associated with community-acquired UTIs in the USA alone exceed an estimated US $1.6 billion. Urinary tract infections account for more than 100,000 hospital admissions annually, most often for pyelonephritis. They also account for at least 40% of all hospital-acquired infections and are in the majority of cases catheter-associated. Nosocomial bacteriuria develops in up to 25% of patients requiring a urinary catheter for > 7 days, with a daily risk of 5%. It has been estimated that an episode of nosocomial bacteriuria adds US $500-1,000 to the direct cost of acute-care hospitalization. In addition, the pathogens are fully exposed to the nosocomial environment, including selective pressure by antibiotic or antiseptic substances. Nosocomial UTIs therefore comprise perhaps the largest institutional reservoir of nosocomial antibiotic-resistant pathogens.

Classification of Urinary Tract Infections

Infections can be classified according to their location within the urinary tract, e.g. pyelonephritis, cystitis. The different parts of the urinary tract, however, communicate with each other to some degree. As a result, bacteria in one area are probably also present elsewhere. For practical clinical reasons, UTIs are classified according to the predominant clinical symptoms:

  • uncomplicated lower UTI (cystitis)
  • uncomplicated pyelonephritis
  • complicated UTI with or without pyelonephritis
  • urosepsis

The clinical presentation and management of different UTI categories may vary during life and may depend on the patient’s condition. Therefore, special patient groups (the elderly, those with underlying diseases and the immunocompromised) have also to be considered.

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Pathogenesis of Urinary Tract Infections

Micro-organisms can reach the urinary tract by haematogenous or lymphatic spread, but there is abundant clinical and experimental evidence to show that the ascent of micro-organisms from the urethra is the most common pathway leading to a UTI, especially organisms of enteric origin (i.e. Escherichia coli and other Enterobacteriaceae). This provides a logical explanation for the greater frequency of UTIs in women than in men and for the increased risk of infection following bladder catheterization or instrumentation. A single insertion of a catheter into the urinary bladder in ambulatory patients results in urinary infection in 1-2% of cases. Indwelling catheters with open-drainage systems result in bacteriuria in almost 100% of cases within 3-4 days. The use of a closed-drainage system, including a valve preventing retrograde flow, delays the onset of infection, but ultimately does not prevent it. It is thought that bacteria migrate within the mucopurulent space between the urethra and catheter, and that this leads to the development of bacteriuria in almost all patients within about 4 weeks.

Haematogenous infection of the urinary tract is restricted to a few relatively uncommon microbes, such as Staphylococcus aureusCandida spp., Salmonella spp. and Mycobacterium tuberculosis, which cause primary infections elsewhere in the body.Candida albicans readily causes a clinical UTI via the haematogenous route, but is also an infrequent cause of an ascending infection if an indwelling catheter is present or following antibiotic therapy. The concept of bacterial virulence or pathogenicity in the urinary tract infers that not all bacterial species are equally capable of inducing infection. The more compromised the natural defence mechanisms (e.g. obstruction, bladder catheterization), the fewer the virulence requirements of any bacterial strain to induce infection. This is supported by the well-documented in-vitro observation that bacteria isolated from patients with a complicated UTI frequently fail to express virulence factors. The virulence concept also suggests that certain bacterial strains within a species are uniquely equipped with specialized virulence factors, e.g. different types of pili, which facilitate the ascent of bacteria from the faecal flora, introitus vaginae or periurethral area up the urethra into the bladder, or, less frequently, allow the organisms to reach the kidneys to induce systemic inflammation.

Microbiological and Other Laboratory Findings

The number of bacteria is considered relevant for the diagnosis of a UTI. In 1960, Kass developed the concept of ’significant‘ bacteriuria (≥ 105 cfu) in the context of pyelonephritis in pregnancy. Although this concept introduced quantitative microbiology into the diagnostics of infectious diseases and is therefore still of general importance, it has recently become clear that there is no fixed number of significant bacteriuria, which can be applied to all kinds of UTIs and in all circumstances. Sterile pyuria is defined as the presence of leukocytes without bacteria.  The following bacterial counts are clinically relevant:

  • ≥ 103 colony-forming units (cfu) of uropathogen/mL of a mid-stream sample of urine in acute uncomplicated cystitis in a woman
  • ≥ 104 cfu uropathogen/mL of mid-stream sample of urine in acute uncomplicated pyelonephritis in a woman
  • ≥ 105 cfu uropathogen/mL of mid-stream sample of urine in a woman, or ≥ 104 cfu uropathogen/mL of mid-stream sample of urine in a man or in straight catheter urine in women in a complicated UTI.

 In a suprapubic bladder puncture specimen, any count of bacteria is relevant. Asymptomatic bacteriuria is diagnosed if two cultures of the same bacterial strain (in most cases the species only is available) taken ≥ 24 hours apart show bacteriuria of ≥ 105 cfu uropathogen/mL.

In clinical routine assessment, a number of basic criteria must be looked at before a diagnosis can be established, including:

  • clinical symptoms
  • results of selected laboratory tests (blood, urine)
  • evidence of the presence of microbes by culturing or other specific tests.

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References

1. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113(Suppl 1A):5S-13S. [PubMed]  

2. Gales AC, Jones RN, Gordon KA, Sader HS, Wilke WW, Beach ML, Pfaller MA, Doern GV. Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998). J Antimicrob Chemother 2000;45:295-303.  [PubMed]

3. Kass EH. Bacteriuria and pyelonephritis of pregnancy. Arch Intern Med 1960;105:194-198. [PubMed]

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6. Naber KG, Bergman B, Bjerklund-Johansen TE, Botto H, Lobel B, Jiminez Cruz F, Selvaggi FP; Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). EAU guidelines for the management of urinary and male genital tract infections. Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). Eur Urol 2001;40:576-588. [PubMed]

7. Naber KG, Bishop MC, Bjerklund-Johansen TE, Botto H, Cek M, Grabe M, Lobel B, Palou J, Tenke P. EAU guidelines on the management of urinary and male genital tract infections. EAU Working Group on Urinary and Male Genital Tract Infections. European Association of Urology (EAU) Guidelines Office. 2006 edition. 1-126. 

8. Patton JP, Nash DB, Abrutyn E. Urinary tract infection: economic considerations. Med Clin North Am 1991;75:495-513.  [PubMed]

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None

Naber KG, Wagenlehner FME. Urinary Tract Infections

Weiskopf J, et al.  Asymptomatic Bacteriuria, What Are you Treating?  JAMA Intern Med 2015:175;344-345.

Leis JA, et al. Reducing Antimicrobial Therapy for Asymptomatic Bacteriuria Among Noncatheterized Inpatients: A Proof-of-Concept Study.  Clin Infect Dis 2014;58:980.

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Urinary Tract Infections: General