This document was amended in July 2016 to reflect literature that was released since the original publication of this content in March 2013. This document will continue to be periodically updated to reflect the growing body of literature related to this topic.
KEYWORDS: Urinary tract infection (UTI); cystitis; pyelonephritis; uropathogens; antibiotics.
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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 bacteremias/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.
Urine is generally considered sterile. The urinary system consists of the kidneys, the collecting system (including the renal calyces, pelvis and the ureter), and the bladder (responsible for storage and elimination of urine). In the female, the urethra exits the bladder near the contiguous vaginal area. 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:
Factors Important for the Genesis of UTIs
Bacterial entry. Most UTIs are caused by ascending entry of bacteria from the periurethral area, emphazing the importance of host factors contributing to entry. 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 or neonates. Relapsing hematogenous infections can be secondary to incompletely treated prostatic or kidney parenchymal infections (eg emphysematous pyelonephritis).
Risk factors for UTIs
Bacterial Uropathogenic Factors
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 asto 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.
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 predipose to 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, it is clear that 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.
Natural Defenses of Urinary Tract
Alterations in Host Defense Mechanisms
|Table 1. Potentially Infective Pathogens in the Urinary Tract|
|Common Causative pathogens in Adult UTIs|
|E. Coli (80% of outpatient UTIs)|
|Staphylococcus saprophyticus (5 – 15%)|
|Adenovirus type 11|
|Normal Perineal Flora:|
Diagnosis of UTI
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 common form of UTI is cystitis (bladder infection) characterized by irritative symptoms such as urinary urgency, frequency, dysuria, hematuria, foul- smelling urine, and suprapubic pain. These symptoms are also typical for urethritis and prostatitis in addition to cystitis. An associated epididymitis, diagnosed reliably by physical examination in men, is an easily localizable variation of UTI. 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.
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 a single bacteria correlate well with urine obtained by other more invasive methods.
A positive chemical (dipstick) leukocyte esterase is 64 – 90% specific and has a similar level of sensitivity for UTI. The finding of nitrite positivity on urine dipstick, indicating the conversion of nitrate to nitrite by certain gram negative bacteria (not gram positive), is very specific but only about 50% sensitive for a urinary tract infection. 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 less specific for a UTI.
Quantitative Urine Culture
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.
Methods to Localize Infection
Used historically to diagnose prostatitis, several localization methods have been described, but are otherwise uncommonly used. Upper urinary tract infections may be isolated using the Stamey test in which the bladder urine is cultured after catheterization, 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.
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, and 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.
Correctable GU Abnormalities that cause Bacterial Persistence
Indications for Radiologic Imaging with UTI
Patients with uncomplicated cystitis or uncomplicated pyelonephritis generally do not benefit from imaging studies to evaluate for potential anatomic abnormalities. In patients who do not respond to treatment, or in patients with predisposing factors, imaging with kidney and bladder ultrasound, or a non-contrast CT scan of the abdomen and pelvis may be useful. Cystoscopic or ureteroscopic evaluation of the urinary tract is not typically performed with uncomplicated UTI or pyelonephritis.
Management of UTI
The combination of clinical findings and urine evaluation 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, 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 (if known), 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.
Highest mean urine concentration (from highest to lowest):
Cabrenicillin > Cephalexin > Ampicillin > TMP/SMX > Cipro > Nitrofurantoin
However, in cases of pyelonephritis, prostatitis or epididymitis, proper tissue antibiotic concentrations are 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 which 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. These factors include: Obstructed urinary flow due to congenital causes, prostatic obstruction or urinary stones; incomplete bladder emptying due to anatomic (prostatic or urethral) or neurogenic (congenital or acquired spinal cord abnormalities) reasons; vesicoureteral reflux, foreign bodies in the urinary tract (instruments, catheters, drainage tubes); systemic illness such as diabetes; pregnancy and males participating in anal intercourse.
Of note, often local antibiograms will be useful for determining the prevalence of local resistance patterns and determining optimal antibiotic strategies, particularly for nosocomial infections.
Additionally, use of antibiotics in pregnancy should be tailored according to the American Board of Obstetrics and Gynecology committee opinion and local consultation with the treating obstetrician is often necessary to determine an optimal and safe strategy for therapy: http://www.acog.org/-/media/Committee-Opinions/Committee-on-Obstetric-Practice/co494.pdf?dmc=1.
Uncomplicated UTI (cystitis, some pyelonephritis)
Other Uncomplicated UTI
Complicated UTI (acute pyelonephritis)
Acute Pyelonephritis with Intrarenal, Perirenal or Pararenal Abscess
Acute Bacterial Prostatitis
Chronic Bacterial Prostatitis
Pontari, M. AUA Core Curriculum for Residents "Urinary Tract Infections"
Shoskes, D. (2011): Urinary Tract Infections Retrieved From: The American Urological Association Educational Review Manual in Urology: 3rd Edition Chapter: 23 Page: 737-766
Smith's General Urology 16th edition 2004. Tanagho and McAninch, eds. Chapter 13. "Bacterial Infections of the Urinary Tract" Nguyen, Hiep. pp. 203 – 227.
Stamm, WE, Norrby, SR. Urinary Tract Infections: Disease Panorama and Challenges. J Infect Dis. 2001 Mar 1; 183 Suppl 1:S1-4.
Hooten, TM, Scholes, D, Hughes, JP, et al. A Prospective Study of Risk Factors for Symptomatic Urinary Tract Infection in Young Women. NEJM 1996; 335: 468-74
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE; 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 inwomen: 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.
Gina Badalato, MD
Disclosures: Nothing to disclose
Melissa Kaufmann, MD
West Palm Beach, FL
Disclosures: Boston Scientific, Other; Cook Myosite, Other
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