Condition

Cystitis and Upper Urinary Tract Infections (UTI) in Male Adults

Editors: Dimitri M. Drekonja MD, MS, FACP, FIDSA; Sigal Yawetz MD; Zbigniew Fedorowicz PhD, MSc, DPH, BDS, LDSRCS; Paritosh Prasad MD

American College of PhysiciansProduced in collaboration with American College of Physicians
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Background Information

Description

  • Cystitis and upper urinary tract infections (UTIs) are infections of the urinary bladder or kidney in male patients.
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  • UTIs in male adults are considered complicated by definition.
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  • Generally these infections occur in patients whose defense mechanisms are impaired by structural or functional abnormalities of the urinary tract.
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Definitions

  • Classification of urinary tract infections (UTIs) in male adults:
    • Asymptomatic bacteriuria:
      • ≥ 105 CFU/mL of single bacterial strain isolated from single urine specimen in an asymptomatic male patient
      • For catheterized male adults, bacteriuria ≥ 105 CFU/mL of a single bacterial strain from a single catheterized specimen likely represents true bacteriuria, but counts as low as ≥ 102 CFU/mL may also be used
    • Acute cystitis is an acute infection of the urinary bladder.
    • Acute pyelonephritis is an acute infection of the kidney.
    • PubMed30895288Clinical infectious diseases : an official publication of the Infectious Diseases Society of AmericaClin Infect Dis201905026810e83-e110e83 References -
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      , N Engl J Med 2012 Mar 15;366(11):1028, commentary can be found in N Engl J Med 2012 Jul 12;367(2):185, Clin Infect Dis 2019 May 2;68(10):e83
  • Recurrent urinary tract infection refers to a symptomatic UTI following clinical resolution of an earlier UTI, typically after treatment which may be due to either:
    • Relapse which is a repeat infection occurring < 2 weeks after treatment that is caused by the same bacteria as the initial infection
    • Reinfection which is a new infection occurring > 2 weeks after treatment of initial infection
    • Reference - Int J Antimicrob Agents 2001 Apr;17(4):259

Epidemiology

Incidence/Prevalence

  • UTIs are more common in young female patients than in young male patients.
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  • The incidence increases in male adults aged ≥ 60 years, primarily due to structural and functional abnormalities (for example, benign prostatic hyperplasia) causing urinary obstruction and turbulence.
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  • Reported community incidence of UTI:
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    • 0.9-2.4 cases per 1,000 male patients aged < 55 years
    • 7.7 cases per 1,000 male adults aged ≥ 85 years
  • Asymptomatic bacteriuria (ASB) is rare among young male adults, but increases with age:
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    • Reported in 10% of community dwelling male adults aged > 80 years
    • Reported in 15%-40% of male residents of long-term care facilities
  • STUDY SUMMARY
    annual incidence of UTI in males 2.3% and lifetime prevalence approximately 14%
    COHORT STUDY: J Urol 2005 Apr;173(4):1288

Risk Factors

  • Benign prostatic hypertrophy is the most common predisposing factor in male adults.
    • Benign prostatic hypertrophy may lead to bladder outlet obstruction and residual urine in the bladder after voiding.
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    • STUDY SUMMARY
      incidence of prostatic hypertrophy 33% in male adults with UTI
      COHORT STUDY: JAMA Intern Med 2013 Jan 14;173(1):62

  • Other risk factors for UTI include:
    • Previous urinary tract surgery
    • Recent procedures, including cystoscopy, catheterization, transrectal prostate biopsy
    • Urinary tract anatomic and physiologic abnormalities leading to incomplete bladder emptying
    • Urethral stricture
      • STUDY SUMMARY
        incidence of urethral stricture 7.7% in male adults with UTI
        COHORT STUDY: JAMA Intern Med 2013 Jan 14;173(1):62

    • Bladder outlet obstruction
    • Institutional care
    • Age > 65 years
    • Having an uncircumcised penis
    • Immunocompromise
    • Engaging in sex with an infected female partner or engaging in anal intercourse
    • References - J Fam Pract 2007 Aug;56(8):657, Curr Opin Infect Dis 2014 Feb;27(1):97
  • STUDY SUMMARY
    previous urinary tract infection associated with increased risk of UTI in males aged ≥ 86 years
    COHORT STUDY: BMC Med 2011 May 16;9:57

Associated Conditions

  • It is unknown how often prostate co-infection occurs in male adults with a UTI.
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  • STUDY SUMMARY
    male adults with febrile UTI may have prostate infection, even without tender prostate
    COHORT STUDY: BJU Int 1999 Sep;84(4):470

  • STUDY SUMMARY
    elevated PSA associated with recurrent UTI
    COHORT STUDY: Prostate 2013 Oct;73(14):1529

Etiology and Pathogenesis

Pathogen

  • Escherichia coli is the most common cause of UTI in male adults with a normal urinary tract.
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  • Other pathogens that may cause UTI in male adults include:
    • Proteus species
    • Providencia species
    • Klebsiella species
    • Enterobacter species
    • Pseudomonas species
    • Citrobacter species
    • Enterococcus faecalis
    • Staphylococcus epidermidis
    • Staphylococcus aureus
    • Reference - Am J Med 1999 Mar;106(3):327
  • Patterns may vary over time and from one facility to another, with multidrug-resistant strains becoming increasingly frequent in male adults living in nursing homes and other institutions.
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Pathogenesis

  • Bacteria is thought to ascend into the urinary tract or enter the bladder through instrumentation.
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  • Pathogens may have more difficulty infecting the urinary tract in male adults compared to female adults due to:
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    • Longer distance between the urethral meatus and the perianal region
    • Longer length of the male urethra
    • Bactericidal activity of prostatic fluid
  • Specific factors involved in adherence and colonization of bladder epithelium by uropathogens:
    • Pili mediate adhesion and tissue invasion:
      • Chaperone-usher pathway (CUP) pili are expressed by many gram-negative bacteria, including uropathogenic Escherichia coli.
      • Adhesins at the tip of the pili recognize specific receptors on the epithelium:
        • Type 1 pili tipped with FimH adhesin:
          • This pili recognizes mannosylated uroplakins and alpha1beta3 integrins.
          • It is essential for colonization and invasion of umbrella cells of bladder epithelium.
          • Type I pili is also involved in biofilm formation.
        • Pyelonephritis-associated (P) pili tipped with PapG adhesin:
          • This pili binds globosides containing glycolipids in kidneys.
          • It also modulates the local immune response and inhibits immunoglobulin (Ig)A transport into urinary space.
        • Pili produced by Proteus mirabilis include:
          • Mannose-resistant Proteus-like (MR/P) pili are involved in biofilm formation and colonization.
          • Other CUP pili with unknown in vivo mechanistic roles include P. mirabilis-like fimbriae (PMFs) and nonagglutinating fimbriae (NAFs).
        • Endocarditis- and biofilm-associated (Ebp) pili tipped with EbpA adhesin is an important adhesion factor in enterococcal UTI.
    • Other adhesins:
      • Autotransporters in P. mirabilis:
        • Trimeric autoagglutinin autotransporter of Proteus (TaaP) binds laminin, which is involved in bladder infection.
        • Adhesion and invasion are mediated by the Proteus autotransporter (AipA) that binds collagen I, which is involved in kidney infection.
      • Enterococcal adhesion factors include collagen adhesin Ace, enterococcal surface protein (Esp), and enterococcal polysaccharide antigen (Epa).
    • Reference - Nat Rev Microbiol 2015 May;13(5);269
  • Other virulence factors:
    • Proteases and toxins:
      • Uropathogenic E. coli:
        • Alpha-hemolysin (HlyA) induces pore formation and lysis in umbrella cells of the bladder epithelium.
        • Cytotoxic necrotizing factor 1 (CNF1) is involved in actin cytoskeleton rearrangement and prevention of apoptosis of colonized cells.
      • P. mirabilis:
        • Hemolysin (HpmA) is involved in pore formation and the destabilization of the host cell.
        • Proteus toxic agglutinin (Pta) becomes functional in an alkaline pH induced by bacterial urease activity, and it punctures the host cell membrane.
      • Pseudomonas aeruginosa:
        • Elastases induce tissue destruction to release nutrients that feed bacterial growth.
        • Exoenzyme S (ExoS) affects cell adherence and morphology.
        • Hemolytic phospholipase C hydrolyzes phosphatidylcholine from the host cell membrane, compromising cell integrity.
    • Urease:
      • Urease is produced by P. mirabilis, S. saprophyticus, K. pneumoniae, P. aeruginosa.
      • Urea elevates urine pH, leading to the formation of calcium crystals and magnesium ammonium phosphate precipitates in urine.
      • Accumulation of ammonia is toxic to uroepithelial cells, leading to direct tissue damage.
    • Siderophores:
      • Siderophore systems are involved in iron scavenging for growth, as the bladder has limited iron.
      • Specific siderophores include:
        • Aerobactin and yersiniabactin in uropathogenic E. coli
        • Pyochelin and pyoverdine in P. aeruginosa
        • Enterobactin and aerobactin in K. pneumoniae
        • Proteobactin and yersiniabactin-related in P. mirabilis
    • Reference - Nat Rev Microbiol 2015 May;13(5);269
  • Escherichia coli virulence factors appear to play role in infection.
    • E. coli strains causing febrile UTI have significantly higher prevalence of virulence-associated phylogenetic groups, serotypes, and extraintestinal virulence genes (hemolysin, cytotoxic necrotizing factor, outer membrane protease T) compared to rectal isolates (Clin Infect Dis 2005 Mar 15;40(6):813).
    • E. coli strains causing pyelonephritis contain higher prevalence of certain virulence genes (papAH, papC, papEF, papGII, papGIII, cnf1, ompT, and usp) compared to those causing cystitis (Clin Microbiol Infect 2013 Apr;19(4):E173).
    • In patients with functional or structural abnormalities of the urinary tract, infections are often caused by less virulent E. coli strains.
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