Lower Urinary Tract Infection

32 Lower Urinary Tract Infection

Mickey M. Karram, Steven D. Kleeman

EPIDEMIOLOGY 413

MICROBIOLOGY 414

PATHOGENESIS 414

Host Factors 415

Bacterial Virulence Factors 415

DEFINITIONS 416

CLINICAL PRESENTATION 416

Urine Collection Methods 416

Urine Microscopy 416

Rapid Diagnostic Tests 417

Urine Culture 417

Radiologic Studies 417

Cystourethroscopy 417

Urodynamic Studies 417

DIFFERENTIAL DIAGNOSIS 417

MANAGEMENT OF LOWER URINARY TRACT INFECTION 418

First infections or Infrequent Reinfections 419

Recurrent Infections 420

Asymptomatic Bacteriuria 421

SEXUAL INTERCOURSE AND DIAPHRAGM USE 421

CATHETER-ASSOCIATED INFECTION 422

LOWER URINARY TRACT INSTRUMENTATION 422

PYELONEPHRITIS 422

Urinary tract infections are a significant health care problem affecting an estimated 10% to 20% of women during their lifetimes and accounting for approximately 7 million office visits per year. Management of a single episode of cystitis costs an estimated $140, and the annual health care costs of urinary tract infections in women are estimated to exceed $1 billion.

In the past 30 years, there have been significant developments in our understanding of the pathogenesis and management of urinary tract infections. These include recognition that about one third of women with cystitis have bacterial counts lower than 100,000 colony-forming units (CFU) per milliliter of urine, realization that bacteria infecting the urinary tract usually come from fecal flora, documentation that most recurrent urinary tract infections are reinfections caused by fecal bacteria and can be successfully managed by low-dose prophylaxis, introduction of newer antimicrobial therapy, and the understanding that certain women with cystitislike symptoms have sterile urine and will ultimately be diagnosed as sensory urgency, overactive bladder, or a painful bladder condition.

EPIDEMIOLOGY

Urinary tract infections are more prevalent among women than men (ratio of 20:1), probably secondary to an anatomically short urethra and its close proximity to the vagina and rectum. Approximately 5 million cases of cystitis occur annually in the United States, and over 100,000 patients are hospitalized every year for renal infection. At least 50% of women experience an episode of cystitis at some time during their lives and about 5% have frequent episodes.

The prevalence of urinary tract infections increases with age. At 1 year, 1% to 2% of female infants demonstrate bacteriuria. In this age group, there is a direct correlation between cystitis and upper urinary tract infection. As many as 50% of these patients demonstrate abnormalities on intravenous pyelograms, such as scarring, ipsilateral reflux, or some obstructive disease. After 1 year of age, the infection rate decreases to approximately 1% and remains low until puberty. Between ages 15 and 24, the prevalence of bacteriuria is about 2% to 3% and increases to about 15% at age 60, 20% after age 65, and 25% to 50% after age 80 (Fig. 32-1). Sexual activity and pregnancy are major factors in younger age groups, whereas pelvic relaxation, systemic illnesses, and hospitalization play major roles in older women. However, the prevalence of underlying urologic abnormalities decreases dramatically with age.

Figure 32-1 Prevalence of bacteriuria in females as a function of age.

(From Karram MM: Lower urinary tract infection. In Ostergard DR, Bent AE, eds: Urogynecology and urodynamics, Baltimore, 1991, Williams & Wilkins.)

Approximately 2% of all patients admitted to a hospital acquire a urinary tract infection, which accounts for 500,000 nosocomial infections per year. One percent of all these infections become life threatening. Instrumentation or catheterization of the urinary tract is a precipitating factor in at least 80% of these infections. The annual cost of nosocomial urinary tract infections is estimated to range between $424 and $451 million. Asymptomatic bacteriuria occurs in 2% to 8% of adult females, the likelihood of which increases with increasing age, diabetes mellitus, and a history of symptomatic urinary tract infection. Symptomatic urinary tract infections are believed to affect over 30% of women between the ages of 20 and 40 years. Patients who develop infections are more likely to develop subsequent infections. The incidence of re-infections seems to be independent of whether an infection was treated or allowed to resolve on its own. It has been shown that the probability of recurrent urinary tract infections increases with the number of previous infections and decreases with greater amount of elapsed time between infections. Rates of reinfection seem to be independent of bladder dysfunction, evidence of chronic pyelonephritis on radiologic examinations, and vesicoureteral reflux. Kraft and Stamey (1977) showed that patients who had two or more urinary tract infections within a 6-month period had a 66% probability of attaining another infection in the next 6 months. Antimicrobial prophylaxis of urinary tract infections does not change the risk of recurrent bacteriuria, but only seems to alter the time until the redevelopment of another urinary tract infection.

MICROBIOLOGY

Gram-negative bacilli of the family Enterobacteriaceae are responsible for 90% of urinary tract infections. Escherichia coli is the single most important organism and accounts for 80% to 90% of uncomplicated infections. Others include Klebsiella, Enterobacter, Serratia, Proteus, Pseudomonas, Providencia, and Morganella species. Pseudomonas aeruginosa infection is almost always secondary to urinary tract instrumentation. Staphylococcus saprophyticus is the second most common cause of cystitis and causes 10% of infections in sexually active females. Staphylococcus epidermidis is a nosocomial pathogen identified in patients with indwelling catheters. Staphylococcus aureus is less commonly isolated and is often secondary to hematogenous renal infection. Other gram-positive organisms such as enterococci and Streptococcus agalactiae cause about 3% of episodes of cystitis. Enterococcus faecalis causes about 15% of nosocomial urinary infections, and Str. agalactiae is more commonly the cause in patients with diabetes mellitus. Anaerobic bacteria, although abundant in fecal flora, rarely cause urinary tract infections. The oxygen tension in the urine probably prevents their growth and persistence in the urinary tract.

Candida albicans and other fungal organisms can cause lower urinary tract infections in patients with diabetes mellitus or indwelling urinary catheters. Immunocompromised patients and recipients of renal transplantation are vulnerable to candidal urinary tract infections. Torulopsis glabrata is second in frequency to C. albicans. Viruria has been documented with many viruses, but generally in association with viremia. Viral urinary tract infections occur as acute illnesses (acute hemorrhagic cystitis in children, polyoma virus infection after bone marrow transplant), during convalescence from viral infections (mumps, cytomegalovirus), and in asymptomatic patients (cytomegalovirus).

PATHOGENESIS

Although the normal female urinary tract is remarkably resistant to infection, certain risk factors for developing urinary tract infections have been identified (Box 32-1). The majority of urinary tract infections are ascending infections wherein the fecal flora initially colonize the vaginal introitus, then the periurethral tissues, and eventually gain entry into the bladder (Fig. 32-2). The development of urinary tract infection requires the interaction of appropriate host susceptibility and pathogen virulence factors (Fig. 32-3).

Figure 32-2 Pathways of bacterial entry into the urinary tract.

(From Karram MM: Lower urinary tract infection. In Ostergard DR, Bent AE, eds: Urogynecology and urodynamics, Baltimore, 1991, Williams & Wilkins.)

Figure 32-3 Factors determining host risk and susceptibility to bacterial cystitis in normal females with anatomically normal urinary tracts.

(From Karram MM: Lower urinary tract infection. In Ostergard DR, Bent AE, eds: Urogynecology and urodynamics, Baltimore, 1991, Williams & Wilkins.)

Host Factors

Several important host defense mechanisms are instrumental in the prevention of urinary tract infections. The normal acidic pH of the vaginal secretions in a premenopausal woman inhibits the growth of enterobacteria such as E. coli and promotes the growth of lactobacilli, diphtheroids, and other gram-positive bacteria—organisms that replicate poorly in urine. Normal periodic voiding with its dilutional effects and the high urea and organic acid concentrations of urine in a setting of a low pH serve as important bladder defense mechanisms. The glycosaminoglycans in the bladder lining and immunoglobulins in the urine are important factors that block bacterial adherence. The deficiency of glycosaminoglycans probably plays a role in recurrent urinary tract infections. In addition, the ascending loop of Henle secretes Tamm-Horsfall protein, a mannose-rich uromucoid that may inhibit bacterial adherence to epithelial cells and trap bacteria in the urine, thereby allowing them to be flushed from the urinary tract.

Studies have shown that women of blood groups B and AB, who are nonsecretors of blood-group substances, are at a greater risk for urinary tract infections, suggesting a possible genetic link. Similarly, a higher prevalence of HLA-A3 subtype was noted among women with recurrent urinary tract infections.

Factors such as sexual activity and diaphragm use are significantly associated with the development of lower urinary tract infections. The frequency and recency of sexual intercourse increase the risk of cystitis. This increase appears to occur through inoculation of periurethral bacteria into the bladder during intercourse. The increased risk associated with diaphragm use may be related to urethral obstruction caused by it as well as the propensity for vaginal colonization by coliforms.

Bacterial Virulence Factors

The adherence of bacteria to mucosal cells appears to be a necessary step for colonization and pathogenicity. E. coli, the most common uropathogen, is the most extensively studied. Three different types of adhesins have been identified: type 1 pili (or fimbriae), P-fimbriae, and X-adhesins. Type 1 pili have a strong affinity for mannose-containing compounds, including Tamm-Horsfall protein, and facilitate attachment of E. coli to vaginal, periurethral, and bladder epithelial cells. P-fimbriae and the less well-studied X-adhesins are important in ascending infections of the kidney. P-fimbriae have a high affinity for P blood group antigens found on erythrocytes and uroepithelial cells. Type 1 pili and P-fimbriae are often possessed by the same bacterium and, after gaining entry to the kidney, the expression of Type 1 pili is turned to avoid phagocytosis. Some type of increased susceptibility of certain host cells to be adhered to also seems possible. Women with certain Lewis blood groups, Le(A−,B−) and Le(A+,b−) phenotypes, have significantly higher rates of recurrent urinary tract infections than women with Le(a−,b+) phenotype. The Lewis antigen controls fucosylation. Premenopausal women are more susceptible to attachment of certain strains of E. coli and lactobacilli during certain times of the menstrual cycle and during early pregnancy.

Bacteria possess a variety of other virulence factors, of which multidrug resistance is most clinically significant. Uropathogens develop resistance primarily through the resistance transfer plasmid. Plasmid resistance has been found for β-lactams, sulfonamides, aminoglycosides, and trimethoprim. So far, no plasmid-mediated resistance has been identified to fluoroquinolones, which makes these agents valuable in treating infections caused by multidrug-resistant bacteria. Other virulence factors include production of hemolysins and colicin V by some enterobacteria and urease by Proteus species.

DEFINITIONS

When discussing urinary tract infections, an understanding of the generally accepted definitions is essential.

Bacteriuria implies the presence of bacteria in the urine. The term includes both renal and bladder bacteriuria. Symptomatic bacteriuria can have as few as 100 CFU/mL, whereas asymptomatic bacteriuria requires the growth of 100,000 CFU/mL.

Urethritis is inflammation of the urethra and requires an adjective for modification (e.g., nongonococcal, nonspecific). In women, symptoms of urethritis are indistinguishable from those of cystitis, and pure urethritis is exceedingly rare.

Trigonitis is inflammation or localized hyperemia of the trigone. Unfortunately, this term is often misused to describe the normal cobblestone or granular appearance of the trigone seen on cystoscopy. Embryologically, this represents squamous metaplasia because the trigone is a derivative of the müllerian system, unlike the rest of the bladder.

Cystitis indicates inflammation of the bladder and can be used as a histologic, cystoscopic, bacteriologic, or clinical term. Bacterial cystitis must be differentiated from nonbacterial cystitis (i.e., radiation or interstitial cystitis).

Pyelonephritis is a clinical term that refers to a syndrome of chills, fever, and flank pain accompanied by bacteriuria and pyuria.

Uncomplicated is a term used to describe an afebrile infection in a patient with a structurally and functionally normal urinary tract. The majority of episodes of isolated or recurrent cystitis in women are uncomplicated and can be eradicated easily by a short course of inexpensive antimicrobial therapy.

Complicated infections are those in patients with pyelonephritis or a urinary tract with structural or functional abnormality. These infections are often caused by bacteria that demonstrate multiple drug resistance.

Chronic, as it pertains to infection, is a poorly defined term that is best avoided.

Prophylactic antimicrobial therapy is the use of antimicrobial drugs for the prevention of reinfection of the urinary tract. It assumes that bacteria have been completely eliminated before the initiation of prophylaxis.

Suppressive antimicrobial therapy refers to suppression of an existing infection that the clinician is unable to eradicate. Suppression may result in abacteriuric urine or may reduce the bacterial load without achieving sterile urine.

Reinfection describes recurrent infection with different bacteria from outside the urinary tract. This is essentially a new event, with the urine showing no growth after the preceding infection. Reinfections are often caused by the same species, such as E. coli, that continue to colonize the vaginal introitus.

Relapse refers to consecutive urinary tract infections caused by the same bacterial strain from a focus within the urinary tract such as a stone. Unfortunately, some investigators use the term with a 2-week or shorter limitation between recurrences, implying that the kidney is the site of bacterial relapse when ascending reinfections from the urethra or vagina can also readily recur within 2 weeks.

Persistence of bacteria implies the continued presence of the same infecting microorganisms isolated at the start of treatment. This can be caused by several factors, including an underlying structural or functional abnormality, bacterial resistance, inadequate drug dosage, or poor patient compliance.

CLINICAL PRESENTATION

The symptoms and signs of urinary tract infections in women are diverse. Lower urinary irritative symptoms associated with cystitis are dysuria, frequency, urgency, nocturia, and suprapubic discomfort. Occasionally, mild incontinence and hematuria may occur. Gross hematuria is rare. Systemic symptoms are usually absent. Upper urinary tract infections commonly appear with fever, chills, malaise, and occasionally nausea and vomiting. Flank pain and costovertebral angle tenderness are usually present. The pain is colicky if acute pyelonephritis is complicated by a renal calculus or a sloughed renal papilla secondary to diabetic or analgesic nephropathy.

DIAGNOSIS

Urine Collection Methods

Considerable care should be taken when collecting urine from ambulatory patients. To minimize contamination, women should be instructed to spread the labia; to wipe the periurethral area from front to back with a clean, moistened gauze sponge; and to collect a midstream urine sample while holding the labia apart. Certain patients with physical disability or obesity are unable to obtain a clean voided specimen. In such women, urethral catheterization or suprapubic aspiration of the bladder can be performed. However, urethral catheterization is not without risks. Catheter infection rates range from 1% in healthy young women to 20% in hospitalized patients.

Urine Microscopy

Microscopic examination of urine adds valuable information to the diagnosis and evaluation of urinary tract disorders. A thorough microscopic examination of an uncentrifuged sample of urine can detect the presence of significant bacteria, leukocytes, and red blood cells. In a random urine sample, pyuria is defined as more than 10 white blood cells/mL of urine and is assessed using a hemocytometer. In a clinical setting with symptoms suggestive of urinary tract infection, pyuria and hematuria offer sufficient supportive evidence to warrant empirical antibiotic therapy. In the absence of pyuria, the diagnosis of urinary tract infection should be questioned. Some examples of abacterial or sterile pyuria are tuberculosis, renal calculi, glomerulonephritis, interstitial cystitis, and chlamydial urethritis.

Microscopic hematuria is found in 40% to 60% of cases of acute cystitis and is specific for cystitis in women with dysuria. Microscopic bacteriuria, using uncentrifuged Gram-stained urine, is found in over 90% of urinary tract infections with colony counts of 100,000 CFU/mL or more and is a highly specific finding. However, bacteria are not readily detectable in lower colony-count infections, such as 100 to 10,000 CFU/mL. Thus, microscopic hematuria and bacteriuria lack sensitivity but are highly specific for urinary tract infections.

Rapid Diagnostic Tests

Rapid diagnostic tests are generally less accurate than urine microscopy but are convenient and cost-effective. The most common rapid detection test is the nitrite test, based on the bacterial conversion of nitrates to nitrite. Often integrated with it is the esterase test, which detects the presence of leukocyte esterase, suggesting pyuria. The sensitivity of these tests is 60% in bacterial counts greater than 100,000 CFU/mL and only 22% in infections with bacterial counts of 10,000 to 100,000 CFU/mL. The test is ideally performed on first morning voided specimens to minimize false-negative results. False-negative results can also occur in enterococcal infections and in the presence of certain dyes such as bilirubin, methylene blue, and phenazopyridine.

Only gold members can continue reading. Log In or Register to continue

Related

Stay updated, free articles. Join our Telegram channel

Tags: Urogynecology and Reconstructive Pelvic Surgery

Mar 10, 2016 | Posted by admin in Reconstructive surgery | Comments Off

Full access? Get Clinical Tree

Get Clinical Tree app for offline access

Get Clinical Tree app for offline access