Infections of the Urinary Tract

Published on 08/02/2015 by admin

Filed under Basic Science

Last modified 08/02/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 4178 times

Infections of the Urinary Tract

Objectives

1. Describe the anatomy and identify the structures of the urinary tract, for both males and females.

2. Name the organisms that colonize the urethra and are considered normal flora.

3. Explain how the female urinary tract anatomy may predispose women to urinary tract infections.

4. Differentiate between community-acquired urinary tract infections and hospital-acquired urinary tract infections.

5. List the routes of transmission that allow bacteria to invade and cause a urinary tract infection.

6. Name the physical and chemical properties of urine that contribute to its role in the body’s defense mechanism against the bacteria capable of causing urinary tract infections.

7. Explain host and microbial factors that determine whether bacteria will be able to colonize and cause a urinary tract infection.

8. Name the properties bacteria possess that predispose them to having greater pathogenicity in causing urinary tract infections.

9. Define the five major types of urinary tract infections: pyelonephritis, cystitis, urethritis, acute urethral syndrome, and asymptomatic bacteriuria.

10. Compare and contrast complicated and uncomplicated urinary tract infections.

11. Explain the collection methods for urine specimens, including clean catch midstream urine, straight catheterized urine, a suprapubic bladder aspiration, and an indwelling catheter collection.

12. Describe the urine-screening methods available to determine bacteriuria and pyuria.

13. Explain the nitrate reductase test, the leukocyte esterase test, and the catalase test in regard to their urine-screening capability.

14. Name the media required for urine cultures.

15. Explain the proper methodology for plating and interpreting a quantitative urine culture.

16. Correlate signs and symptoms with the results of laboratory diagnositc procedures for the identification of the etilogic agent associated with infections of the urinary tract.

General Considerations

Anatomy

The urinary tract consists of the kidneys, ureters, bladder, and urethra (Figure 73-1). The function of the urinary tract is to make and process urine. Urine is an ultrafiltrate of blood that consists mostly of water but also contains nitrogenous wastes, sodium, potassium, chloride, and other analytes. Urine is normally a sterile fluid, Often, urinary tract infections (UTIs) are characterized as being either upper (U-UTI) or lower (L-UTI) based primarily on the anatomic location of the infection: the lower urinary tract encompasses the bladder and urethra, and the upper urinary tract encompasses the ureters and kidneys. Upper urinary tract infections affect the ureters (ureteritis) or the renal parenchyma (pyelonephritis). Lower urinary tract infections may affect the urethra (urethritis), the bladder (cystitis), or the prostate in males (prostatitis).

The anatomy of the female urethra is of particular importance to the pathogenesis of UTIs. The female urethra is relatively short compared with the male urethra and also lies in close proximity to the warm, moist, perirectal region, which is teeming with microorganisms. Because of the shorter urethra, bacteria can reach the bladder more easily in the female host, thus urinary tract infections are primarily a disorder of women. For men, the incidence of urinary tract infections increases after the age of 60, when the enlargement of the prostate interferes with the removal of urine from the bladder.

Resident Microorganisms of the Urinary Tract

The urethra has resident microflora that colonize its epithelium in the distal portion; these organisms are lactobacilli, corynebacteria, and coagulase-negative staphylococci (Box 73-1). Potential pathogens, including gram-negative aerobic bacilli (primarily Enterobacteriaceae) and occasional yeasts, are also present as transient colonizers. All areas of the urinary tract above the urethra in a healthy human are sterile. Urine is typically sterile, but noninvasive methods for collecting urine must rely on a specimen that has passed through a contaminated milieu. Therefore, quantitative cultures for the diagnosis of UTIs have been used to discriminate among contamination, colonization, and infection.

Infections of the Urinary Tract

Epidemiology

UTIs are among the most common bacterial infections that lead patients to seek medical care. It has been estimated that more than 7 million outpatient visits, 1 million visits to the emergency department, and 100,000 hospital stays every year in the United States are due to UTIs. Approximately 10% of humans will have a UTI at some time during their lives. Of note, UTIs are also the most common hospital-acquired infection, accounting for as many as 35% of nosocomial infections.

The exact prevalence of UTIs is age and sex dependent. During the first year of life, UTIs are less than 2% in males and females. The incidence of UTIs among males remains relatively low after 1 year of age and until approximately 60 years of age when enlargement of the prostate interferes with emptying of the bladder. Extensive studies have shown that the incidence of bacteriuria (presence of bacteria in urine) among girls 5 through 17 years of age is 1% to 3%. The prevalence of bacteriuria in females increases gradually with time to as high as 10% to 20% in older women. In women between 20 and 40 years of age who have had UTIs, as many as 50% may become reinfected within 1 year. The association of UTIs with sexual intercourse may also contribute to this increased incidence because sexual activity increases the chances of bacterial contamination of the female urethra. Finally, as a result of anatomic and hormonal changes that favor development of UTIs, the incidence of bacteriuria increases during pregnancy. These infections can lead to serious infections in both mother and fetus.

UTIs are important complications of diabetes, renal disease, renal transplantation, and structural and neurologic abnormalities that interfere with urine flow. In 40% to 60% of renal transplant recipients, the urinary tract is the source of bacteremia, and in these patients, the recurrence rate is about 40%. In addition, UTIs are a leading cause of gram-negative sepsis in hospitalized patients and are the origin for about half of all nosocomial infections caused by urinary catheters.

Etiologic Agents

Community-Acquired

Escherichia coli is by far the most frequent cause of uncomplicated community-acquired UTIs. At the molecular level, the E. coli, designated uropathogenic E. coli (UPEC), that causes UTIs is sufficiently different from other types of E. coli. Other bacteria frequently isolated from patients with UTIs are Klebsiella spp., other Enterobacteriaceae, Staphylococcus saprophyticus, and enterococci. In more complicated UTIs, particularly in recurrent infections, the relative frequency of infection caused by Proteus, Pseudomonas, Klebsiella, and Enterobacter spp. increases. In addition, community-acquired urinary tract infections are increasingly associated with multidrug-resistant organisms such as extended β-lactamase-resistant E. coli.

Hospital-Acquired

The hospital environment plays an important role in determining the organisms involved in UTIs. Hospitalized patients are most likely to be infected by E. coli, Klebsiella spp., Proteus spp., staphylococci, other Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, and Candida spp. The introduction of a foreign body into the urinary tract, especially one that remains in place for an extended period (e.g., Foley catheter), carries a substantial risk of infection, particularly if obstruction is present. Thirty five percent of all hospital-acquired infections are urinary tract infections. Eighty percent of those infections are associated with the use of an indwelling catheter. Consequently, UTI is the most common nosocomial infection in the United States, and the infected urinary tract is the most frequent source of bacteremia.

Miscellaneous

Other less frequently isolated agents are other gram-negative bacilli, such as Acinetobacter and Alcaligenes spp., other Pseudomonas spp., Citrobacter spp., Gardnerella vaginalis, Aerococcus urinae, and beta-hemolytic streptococci. Bacteria such as mycobacteria, Chlamydia trachomatis, Ureaplasma urealyticum, Campylobacter spp., Haemophilus influenzae, Leptospira, and certain Corynebacterium spp. (e.g., C. renale) are rarely recovered from urine. Because renal transplant recipients are immunosuppressed, these patients not only suffer from common uropathogens but are also susceptible to opportunistic infections with unusual pathogens. A study involving renal transplant recipients showed that for culture-negative urine, amplification of regions in bacterial 16S rRNA and subsequent analysis by high-performance liquid chromatography detected the presence of a number of known uropathogens as well as unusual agents. Salmonella spp. may be recovered during the early stages of typhoid fever; their presence should be immediately reported to the physician. If anaerobes are suspected, the physician should perform a percutaneous bladder tap unless urine can be obtained from the upper urinary tract by another means (e.g., from a nephrostomy tube). Communication by the clinician to the laboratory that such an agent is suspected is important for detecting such agents. In patients with “sterile pyuria,” Gram stain may reveal unusual organisms with distinctive morphology (e.g., H. influenzae, anaerobes). The presence of any organisms on smear that do not grow in culture is an important clue to the cause of the infection. The laboratory can then take the action necessary to optimize chances for recovery.

In general, viruses and parasites are not usually considered urinary tract pathogens. Trichomonas vaginalis may occasionally be observed in urinary sediment, and Schistosoma haematobium can lodge in the urinary tract and release eggs into the urine. Adenoviruses types 11 and 21 have been implicated as causative agents in hemorrhagic cystitis in children.

Pathogenesis

Routes of Infection

Bacteria can invade and cause a UTI via three major routes: ascending, hematogenous, and lymphatic pathways. Although the ascending route is the most common course of infection in females, ascent in association with instrumentation (e.g., urinary catheterization, cystoscopy) is the most common cause of hospital-acquired UTIs in both sexes. For UTIs to occur by the ascending pathway, enteric gram-negative bacteria and other microorganisms that originate in the gastrointestinal tract must be able to colonize the vaginal cavity or the periurethral area. Once these organisms gain access to the bladder, they may multiply and then pass up the ureters to the kidneys. UTIs occur more often in women than men, at least partially because of the short female urethra and its proximity to the anus. As previously mentioned, sexual activity can increase chances of bacterial contamination of the female urethra.

In most hospitalized patients, UTI is preceded by urinary catheterization or other manipulation of the urinary tract. The pathogenesis of catheter-associated UTI is not fully understood. It is certain that soon after hospitalization, patients become colonized with bacteria endemic to the institution, often gram-negative aerobic and facultative bacilli carrying resistance markers. These bacteria colonize the patient’s skin, gastrointestinal tract, and mucous membranes, including the anterior urethra. With insertion of a catheter, the bacteria may be pushed along the urethra into the bladder or, with an indwelling catheter, may migrate along the track between the catheter and the urethral mucosa, gaining access to the bladder. It is estimated that approximately 10% to 30% of catheterized patients will develop bacteriuria (presence of bacteria in urine).

UTIs may also occur by the hematogenous, or blood-borne, route. Hematogenous spread usually occurs as a result of bacteremia. Any systemic infection can lead to seeding of the kidney, but certain organisms, such as Staphylococcus aureus or Salmonella spp., are particularly invasive. Although most infections involving the kidneys are acquired through the ascending route, yeast (usually Candida albicans), Mycobacterium tuberculosis, Salmonella spp., Leptospira spp., or Staphylococcus aureus in the urine often indicates pyelonephritis acquired via hematogenous spread, or the descending route. Hematogenous spread accounts for less than 5% of UTIs.

Finally, increased pressure on the bladder can cause lymphatic flow into the kidneys, resulting in UTI. However, evidence for the significance of this potential route is insufficient, indicating that the ascending route remains the major mechanism for the development of UTI.

The Host-Parasite Relationship

Many individuals, women in particular, are colonized in the vaginal or periurethral area with organisms originating from the gastrointestinal tract, yet they do not develop urinary infections. Whether an organism is able to colonize and then cause a UTI is determined in large part by a complex interplay of host and microbial factors.

In most cases, the host defense mechanisms are able to eliminate the organisms. Urine itself is inhibitory to some of the urethral flora such as anaerobes. In addition, if urine has a low pH, high or low osmolality, high urea concentration, or high organic acid content, even organisms capable of growth in the urinary tract may be inhibited. If bacteria do gain access to the bladder, the constant flushing of contaminated urine from the body either eliminates bacteria or maintains their numbers at low levels. Clearly, any interference with the act of normal voiding, such as mechanical obstruction resulting from kidney stones or strictures, will promote the development of UTI. Also, the bladder mucosal surface has antibacterial properties. If the infection is not eradicated, the site of infection remains in the superficial mucosa; deep layers of the bladder are rarely involved.

In addition to the previously described host defenses, a valvelike mechanism at the junction of the ureter and bladder prevents the reflux (backward flow) of urine from the bladder to the upper urinary tract. Therefore, if the function of these valves is inhibited or compromised in any way, such as by obstruction or congenital abnormalities, urine reflux provides a direct route for organisms to reach the kidney. Hormonal changes associated with pregnancy and their effects on the urinary tract increase the chance for urine reflux to the upper urinary tract.

Activation of the host immune response by uropathogens also plays a key role in fending off infection. For example, bacterial contact with urothelial cells initiates an immune response via a variety of signaling pathways. Bacterial lipopolysaccharide (LPS; see Chapter 2) activates host cells to ultimately release cytokines such as tumor necrosis factor and interferon-gamma. In addition, bacteria can activate the complement cascade, leading to the production of biologically active components such as opsonins, as well as augment the host’s adaptive immune response. Host factors that lead to host susceptibility or resistance to uropathogens have been identified. For example, a glycoprotein synthesized exclusively by epithelial cells in a specific anatomic location in the kidney, referred to as Tamm-Horsfall protein or uromodulin, serves as an anti-adherence factor by binding to E. coli–expressing type 1 fimbriae (discussed later). Defensins, a group of small antimicrobial peptides, are produced by a variety of host cells such as macrophages, neutrophils, and cells in the urinary tract and attach to the bacterial cell, eventually causing its death.

Although many microorganisms can cause UTIs, most cases are a result of infection by a few organisms. To illustrate, only a limited number of serogroups of E. coli cause a significant proportion of UTIs. Numerous investigations indicate that UPEC possesses virulence factors that enhance their ability to colonize and invade the urinary tract. Some of these virulence factors include increased adherence to vaginal and uroepithelial cells by bacterial surface structures (adhesins, in particular, pili), alpha-hemolysin production, and resistance to serum-killing activity (Box 73-2). Also, genome sequences of some UPEC strains have been determined, indicating that several potential virulence factor genes associated with the acquisition and development of UTIs are encoded on pathogenicity islands (e.g., hemolysins and E. coli P. fimbriae). Uropathogenic E. coli (UPEC) possess pathogenicity islands containing a variety of virulence factors. By definition, pathogenicity islands (see Chapter 3) contain genes that are associated with virulence and are absent from avirulent or less virulent strains of the same species.

The importance of adherence in the pathogenesis of UTIs has also been demonstrated with other species of bacteria. Once introduced into the urinary tract, Proteus strains appear to be uniquely suited to cause significant disease in the urinary tract. Data indicate that these strains are able to facilitate their adherence to the mucosa of kidneys. Also, Proteus is able to hydrolyze urea via urease production. Hydrolysis of urea results in an increase in urine pH that is directly toxic to kidney cells and also stimulates the formation of kidney stones. Similar findings have been made with Klebsiella spp. Staphylococcus saprophyticus also adheres better to uroepithelial cells than does S. aureus or S. epidermidis.

Other bacterial characteristics may be important in the pathogenesis of UTIs. Motility may be important for organisms to ascend to the upper urinary tract against the flow of urine and cause pyelonephritis. Some organisms demonstrate greater production of K antigen(capsule or outer cell wall); this antigen protects bacteria from being phagocytosed.

Finally, despite numerous host defenses and even antibiotic treatments that can effectively sterilize the urine, a significant proportion of patients have recurrent UTIs. Studies show that uropathogens can invade superficial epithelial cells in the bladder and replicate, forming large foci of intracellular E. coli. This invasion of bladder epithelial cells triggers the host immune response, which in turn causes the superficial cells to exfoliate within hours following infection. Although this exfoliation is considered a host defense mechanism by eliminating infected cells, intracellular organisms are able to reemerge from the bladder epithelial cells and invade the underlying, new superficial layer of epithelial cells, consequently persisting within the urinary tract. Anderson and colleagues reported that intracellular bacteria mature into numerous, large protrusions on the bladder surface they referred to as “pods.” This bacterial organization—in which the intracellular bacteria are embedded in a fibrous, polysaccharide-rich matrix resembling that of a biofilm—may help further explain the persistence of bladder infections despite strong host defenses.

Types of Infection and Their Clinical Manifestations

UTI encompasses a broad range of clinical entities that differ in terms of clinical presentation, degree of tissue invasion, epidemiologic setting, and requirements for antibiotic therapy. There are several types of UTIs: urethritis, ureteritis, asymptomatic bacteriuria, cystitis, the urethral syndrome, and pyelonephritis. Sometimes UTIs are classified as uncomplicated or complicated. Uncomplicated infections occur primarily in otherwise healthy females and occasionally in male infants and adolescent and adult males. Most uncomplicated infections respond readily to antibiotic agents to which the etiologic agent is susceptible. Complicated infections occur in both sexes. In general, individuals who develop complicated infections often have certain risk factors. Some of these risk factors are listed in Box 73-3. In general, complicated infections are more difficult to treat and have greater morbidity (e.g., kidney damage, bacteremia) and mortality compared with uncomplicated infections.

The clinical presentation of UTIs may vary, ranging from asymptomatic infection to full-blown pyelonephritis (infection of the kidney and its pelvis). Some UTI symptoms may be nonspecific, and frequently symptoms overlap considerably in patients with lower UTIs and in those with upper UTIs.

Asymptomatic Bacteriuria

Buy Membership for Basic Science Category to continue reading. Learn more here