Adult UTI AUA 2021
Adult UTI AUA 2021
Adult UTI AUA 2021
LEARNING OBJECTIVES:
At the end of medical school, the student should be able to:
Epidemiology/Socioeconomics/Education
Urinary tract infection (UTI) is a significant health problem in both community and hospital –
based settings. It is estimated that 150 million UTIs occur yearly world-wide, accounting for $6
billion in health care expenditures. In premenopausal women in the U.S., an annual estimated
incidence of UTI is 0.5 – 0.7/person/year. In Medicare beneficiaries 65 years or older, UTIs
account for 1.8 million office visits per year.
The majority of community- acquired UTIs manifest as uncomplicated bacterial cystitis and occur
mainly in females. In the health-care setting, approximately 40% of all nosocomial infections are
UTIs, and most are associated with the use of urinary catheters. There are more than 1 million
catheter-associated UTIs/year in the U.S., and up to 40% of hospital gram negative
bacteremia/year originate as UTIs.
Urinary infections are treated with antibiotics and removal of predisposing factors when possible,
including indwelling catheters. Antibiotic use should be reserved for symptomatic infections and
the decision to proceed with treatment requires thoughtful consideration of collateral impact and
antimicrobial resistance patterns.
Etiology/Pathogenesis
Definitions
Urine is generally considered sterile. The urinary system can be divided into the upper tract,
which consists of the kidneys (renal parenchyma and collecting system) and the ureters, and the
lower urinary tract, which includes the bladder (responsible for storage and elimination of urine),
the urethra (tube through which urine exits the bladder to the outside world), and prostate in men.
In the female, the urethra exits the bladder near the vaginal area, the vagina could contribute to
contamination of urine specimens. In the male, the urethra exits the bladder, passes through the
prostate, and then through the penile urethra. The foreskin when present may contribute to
infection in select instances. When discussing UTI's it is important to distinguish among the
following terms:
Bacterial entry:
Bacteria ascending into the bladder through the urethra is the most common cause of UTIs. There
are several risk factors that may promote or encourage bacterial ascent.
Hematogenous spread is an uncommon cause of UTIs. The organisms most commonly involved
with hematogenous spread are Staphylococcus aureus, Candida species and Mycobacterium
tuberculosis. Hematogenous infection develops most often in immunocompromised patients,
elderly, or neonates. Relapsing hematogenous infections can be secondary to incompletely treated
prostatic or kidney parenchymal infections (e.g. emphysematous pyelonephritis).
A limited number of E. coli serotypes are responsible for the majority of UTIs. Bacteria that cause
infection have increased adhesion, colonization and tissue invasion properties relative to
nonpathogenic bacteria. The mediators of these pathogenic features include pili, cell surface
structures responsible for adhesion to host tissues, which promote colonization and increase
resistance to bacteriocidal host activity. Specifically, Type 1 pili adhere to mannose receptors on
in the urinary epithelial mucopolysaccharide lining as well as polymorphonuclear leukocytes
(PMNs); Uropathogenic E. coli with Type I pili are often associated with cystitis (bladder
infection). P pili are mannose resistant and adhere to renal glycolipid receptors. P pili do not bind
PMNs and are therefore relatively resistant to phagocytosis and clearing by the host immune
system thus most often associated with kidney infections (pyelonephritis). One characteristic of E.
coli that allows it to ascend to the kidney is the phasic variation of Type 1 pili. Intermittent pili
expression decreases opportunity for PMN binding making phagocytosis is less effective. One of
the significant factors in resistance to bactericidal activity involves the expression of K antigen
(capsular polysaccharide) on bacteria. Another mediator, hemolysin, produced by select bacteria,
can augment tissue invasiveness and predispose to infection.
Host Defenses:
Several factors relating to host defenses determine susceptibility to UTIs. Mechanical issues such
as urethral length (female shorter than male), completeness of bladder emptying (leading to
residual urine in the bladder) and the integrity of the natural uretervesical junction "valve"
(leading to vesicoureteral reflux; VUR) are important anatomic issues that predispose to
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UTIs.Biochemical properties are normally important in making bacterial survival difficult in
urine: acid pH, high urea content, and high osmolality. In addition, mucosal mucopolysaccharide
within the lining of the urinary tract as well as systemic and local antibody production may be
protective for UTIs. Finally, there may be a genetic predisposition to UTIs, as certain HLA and
Lewis blood group (non-secretor status) factors may put patients at higher risk due to increased
colonization ability or increased adherence by bacteria to the urinary tract epithelium.
• Periurethral and Urethral Region – Normal flora in these areas contain: lactobacilli,
coagulase negative staph, corynebacterium and streptococci that form barriers against
colonization. Changes in estrogen, low vaginal pH and cervical IgA affect colonization
by normal flora.
• Urine – High osmolality, high urea concentration, low pH, high organic acids are
protective. Glucose in urine may facilitate infections. Tamm Horsfall proteins may be
protective.
• Bladder – Epithelium expresses Toll-like receptors (TLRs) that recognize bacteria and
initiate immune/inflammatory response (PMNs, neutrophils, macrophages,
eosinophils, NK cells, mast cells and dendritic cells). Adaptive immune response then
predominates (T and B lymphocytes). Induced exfoliation of cells also occurs to allow
excretion of bacterial colonization.
• Kidney – Local immunoglobulin/ antibody synthesis in the kidney occurs in response
to infections (IgG, IgA).
• Obstruction – Key factor in increasing susceptibility to UTI but does not necessarily
predispose to infection.
• VUR – Hodson and Edwards (1960) described association of VUR, UTI, and eventual
renal scarring.
• Underlying Disease – Diabetes mellitus (DM), sickle cell disease (SCD),
nephrocalcinosis, gout, analgesic abuse, aging, hyperphosphatemia, and hypokalemia.
o DM: Glycosuria may contribute to severity of infections due to immune
compromise. Majority of infections (80%) are in the upper tracts.
o Papillary Necrosis: due to DM, pyelonephritis, obstruction, analgesics, SCD,
transplant rejections, cirrhosis, dehydration, contrast media, renal vein
thrombosis.
o HIV: UTIs 5x more prevalent in this population and they recur more
frequently.
• Pregnancy – Bacteriuria in pregnancy = 4-7% and incidence of acute clinical
pyelonephritis = 25-35% in untreated patients.
• Spinal Cord injury with High Pressure Bladder – High morbidity and mortality
from bacteriuria.
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Diagnosis of UTI
Clinical Symptoms
Symptoms are very helpful in the diagnosis of a UTI but may not accurately localize the infection
within the urinary tract. In many cases, however, colonization of the urinary tract can be
asymptomatic. The most generic form of UTI is cystitis (bladder infection) characterized by
irritative symptoms (urinary urgency, frequency, dysuria) hematuria, foul- smelling urine, and
suprapubic pain. These symptoms are also common for urethritis and prostatitis. Epididymitis can
be associated with cystitis and diagnosed reliably by physical examination in men. Symptoms
associated with "upper urinary tract" infections, exemplified by pyelonephritis, may include those
typical of cystitis, as well as fever, rigors, flank or abdominal pain, and frequently associated with
nausea and vomiting.
Collection Method
Analysis of the urine is critical in determining the likelihood of infection. The method of urine
collection is important to distinguish between contamination and true colonization. There are 3
commonly used methods of collection: a) clean catch midstream voided urine, b) catheterized
urine and c) suprapubically aspirated urine. The most variable of these three is the midstream
voided urine, especially in females, where contamination of urine by vaginal or perineal
organisms is common during collection. Voided urines that are sterile or contain high colony
counts (>100,000) of single bacteria correlate well with urine obtained by other more invasive
methods.
Urinalysis
A chemical analysis (dipstick) is suggestive for UTI if leukocyte esterase and/or nitrite are
positive. Detection of leukocyte esterase means that there are white blood cells present in the
urine. Leukocyte esterase has a 73-84% specificity and has a 80-92% sensitivity for UTI. The
finding of nitrite positivity on urine dipstick, indicates the conversion of nitrate to nitrite by
certain gram negative bacteria (not gram positive), is very specific (96-99%) but due to
conversion only by Gram negative bacteria, not very sensitive.
Urine Microscopy
Urine microscopy is an important adjunct to the urinalysis. The finding of elevated white blood
cells in the urine (pyuria) is the most reliable indicator of infection (>10 WBC/hpf on spun
specimen) is 95% sensitive but much like the LE on chemical analysis, less specific for a UTI.
Pyuria in the absence of urinary symptoms does not mean UTI is present. Urine microscopy is
important for identification of the presence of squamous epithelial cells. More than 15-20
squamous epithelial cells/hpf on microscopy is suggestive of a contaminated specimen and sterile
straight catheterized specimen may be desired. In addition, bacteria or yeast species may be seen.
UTI can often have associated gross or microscopic hematuria, the number of RBC/hpf should be
quantified and documented; if a patient has a negative culture a hematuria evaluation would need
to be performed.
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Table 1: Sensitivity and Specificity of Indicators of Possible Infections Found on Urinalysis
and Microscopy
LE 79 (73-84) 87 (80-92)
N 49 (41-57) 98 (96-99)
LE or N 88 (82-91) 79 (69-87)
In general, > 100K colonies/mL on urine culture is considered diagnostic for UTI. However, as
mentioned above, the probability of a UTI also depends on the method of collection. In general,
lower colony counts obtained by sterile urethral catheterization or by suprapubic aspiration can
represent true infection, but clean catch, mid-stream urine that harbors < 100K colonies/mL in a
female requires further verification or repeat sampling to confirm a UTI.
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Normal Perineal Flora
• Lactobacillus
• Corynebacterium
• Staphylococcus
• Streptococcus
Anaerobes
For patients who have recurrent UTI, localization may be desired to identify a possible source if
not clear with imaging and cystoscopy. Upper urinary tract infections may be isolated using the
Stamey test in which a patient is catheterized and urine cultures both before and after a thorough
saline wash. If the second, post-wash bladder culture is positive, this may indicate upper tract
bacteria entering the bladder. Combining bladder washing with selective ureteral catherization is a
more precise way to localize the laterality of the upper tract infection.
Used historically to diagnose chronic bacterial prostatitis, several localization methods have been
described, but are otherwise uncommonly used. To diagnose chronic prostatitis, a "four glass"
quantitative culture test can be used. With this method, urine is collected in four separate
containers:
1) an initial voided urine that reflects bacterial activity within the urethra (urethral pathogens)
2) a subsequent, mid-stream urine to evaluate bacteria within the bladder
3) collection of expressed prostatic secretions, captured from the penile urethra while
messaging the prostate with a rectal exam
4) a post-massage voided urine collection that may reflect prostatic bacteria.
Significantly increased bacterial colony counts in the third (expressed prostatic secretion) and
fourth (post-prostatic secretion) cultures are diagnostic of chronic prostatitis. If acute bacterial
prostatitis is suspected a prostatic massage should NOT be performed for concern of bacteremia.
Differential Diagnosis
The differential diagnosis for recurrent UTI is expansive and includes consideration of other types
on non-bacterial infection as well as causes of recurrent UTIs. In addition, it is important to
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consider the differential diagnosis for non-infectious causes of the same symptoms, specifically
urgency, frequency, and dysuria.
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Management of UTI
The combination of clinical findings and urine evaluation is essential for diagnosis of UTI.
Treatment is based upon pathogen identification and the type and degree of clinical illness, as
well as the presence or absence of predisposing host factors. In general, the treatment consists of
hydration, relief of urinary tract obstruction if present, removal of foreign body or catheter if
feasible, and judicious use of antibiotics. The type and duration of antibiotic treatment is
dependent on site of infection (pyelonephritis, cystitis, prostatitis, epididymitis, orchitis), host
factors, and severity of illness. Most antibiotics are highly concentrated in the urine and therefore
are very effective at clearing bacteria from the urinary tract. However, in cases of pyelonephritis,
prostatitis, epididymitis, or orchitis, selection of antibiotic with proper tissue penetration is
important.
When considering treatment, first determine whether the UTI is complicated or uncomplicated in
nature. Uncomplicated infections include acute cystitis in a non-pregnant, premenopausal female,
and acute pyelonephritis in an otherwise healthy patient. Young post-pubertal females are
susceptible to uncomplicated UTIs because of sexual intercourse in combination with delayed
post-coital bladder emptying. Use of diaphragm and spermicidal contraceptives alter the normal
vaginal flora and may allow colonization by pathogenic E. coli.
Complicated UTIs are those that occur when certain predisposing factors are present, but in
general should be considered in pregnant or post-menopausal females and men. Patients with
complicated UTIs are more likely to have medical co-morbidities or conditions with require
special consideration. In addition, they may have a greater variety of pathogenic bacteria, more
drug resistance, and require a longer duration of antibiotic therapy.
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Uncomplicated Cystitis
• Preferred:
o Fosfomycin, 3 gram single po dose
o Nitrofurantoin, 100 mg po bid x 5 days
o Trimethoprim-sulfamethoxazole DS, 1 pill po bid x 3 days
• Alternative
o Ciprofloxacin, 250 mg bid x 3 days
Cystitis in Men
Bacterial Prostatitis
Special Considerations:
Recurrent UTI
With the push towards antibiotic stewardship increased consideration is be given to non-antibiotic
options for UTI prevention. Vaginal estrogen may be useful for post-menopausal women who
have recurrent UTIs. It is established that after menopause there is thinning of the vaginal
epithelium and alkalization; use of vaginal estrogen preparations may reverse these changes.
There is low systemic absorption of vaginal estrogen preparation, but consideration should be
given to individual patients, risks, and patient preference. There are numerous supplements that
may be used for the prevention of UTIs in some patients, though for many of these there is little
supporting evidence and recommendation is based more anecdotally. The 2012 Cochrane review
concluded that cranberry juice can no longer be recommended, and other cranberry preparations
need to have need to be quantified prior to use in clinical studies. The active ingredient of
cranberries is proanthocyanidins (PAC) specifically type A. It has been determined that 36mg of
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PAC are needed to prevent the binding of E coli to urothelial cells. Methenamine hippurate is
metabolized to formaldehyde in acidic urine and bacteriostatic. The 2012 Cochrane review
concluded that there is evidence that methenamine may be useful for short-term prophylaxis.
Vitamin C can be added to acidify urine alone or in combination with methenamine; it may have a
bacteriostatic effect. Finally, both D-Mannose and Probiotics may be useful in the prevention of
infections, but evidence is limited.
However, at times, despite attempts at preventative measures prophylactic antibiotics are required
form management of recurrent UTIs. Any prior cultures should be reviewed to determine if
antibiotic resistance exists. Options for prophylaxis include a post coital or continuous form. If
daily prophylaxis is considered the best option for the patient, it should be continued for a
minimum of 6 months.
**FDA warnings are posted for use of Nitrofurantoin long term due to severe pulmonary and
hepatic long term effects
Asymptomatic Bacteriuria
Patients with indwelling urethral catheter will universally develop bacteriuria over time; 10-25%
of these will develops symptoms. Risk factors included female gender, elderly, DM, error in
catheter care and bacterial colonization of the drainage bag. Pyuria, cloudy appearance, and foul
odor has not been demonstrated to associated with bacteriuria or UTI
(uptodate.com/contents/catheter-assocated-urinary-tract-infection-in-adults)
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• The IDSA in patient with an indwelling catheter (urethral or suprapubic) or CIC or culture
with in 48 hours of catheter removal positive for >10(3) cfu/ml of uropathogenic bacteria
with the following any of the following symptoms: fevers, suprapubic/CVA tenderness,
unexplained systemic symptoms of mental status change, hypotension, systemic
inflammatory response syndrome without other identifiable cause or source of those
symptoms and signs
• The National Health Safety Network (NHSN) defines it as >10(5) cfu/ml of no more then
2 organisms with symptoms of fever, suprapubic tenderness or CVA pain
Summary
References
Concia, E, et al. Clinical evaluation of guidelines and therapeutic approaches in multi drug-
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Grigoryan, L, et al. Diagnosis and Management of Urinary Tract Infections in the Outpatient
Setting. JAMA 2014;312(16):1677-1684
Gupta, K, et al. Infectious Diseases Society of America; European Society for Microbiology and
Infectious Diseases. (2011). International clinical practice guidelines for the treatment of acute
uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases
Society of America and the European Society for Microbiology and Infectious Diseases. Clin
Infect Dis. Mar 1;52(5):e103-20.
Hooton, T., Acute complicated urinary tract infection (including pyelonephritis) in adults.
Retrieved from https://www.uptodate.com/contents/acute-complicated-urinary-tract-infection-
including-pyelonephritis-in-adults
Hooten, TM, et al. A Prospective Study of Risk Factors for Symptomatic Urinary Tract Infection
in Young Women. NEJM 1996; 335: 468-74
Nguyen, H. (2013) Bacterial Infections of the Urinary Tract. In Tanagho and McAninch, (eds)
Smith & Tanagho’s General Urology (pp 203-227). McGraw-Hill Companies, Inc.
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Pontari, M. AUA Core Curriculum: Urinary Tract Infection. Retrieved from
https://university.auanet.org/core_topic.cfm?coreid=92
Stamey, TA, et al. The Localization and Treatment of Urinary Tract Infections: The Role of
Bactericidal Urine Levels as Opposed to Serum Levels. MEDICINE 44(1); 1-36. January 1965.
Stamm, WE, Norrby, SR. Urinary Tract Infections: Disease Panorama and Challenges. J Infect
Dis. 2001 Mar 1; 183 Suppl 1:S1-4.
Brusch, J, Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females. Retrieved
from https://emedicine.medscape.com/article/233101-overview
Authors
2019
Elizabeth Takacs, MD
Iowa City, IA
Disclosures: Nothing to disclose
2016
Gina Badalato, MD
Scarsdale, NY
Disclosures: Nothing to disclose
Melissa Kaufmann, MD
West Palm Beach, FL
Disclosures: Boston Scientific, Other; Cook Myosite, Other
© 2013, 2016, 2019 American Urological Association Education and Research, Inc.® All Rights
Reserved
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