Urinary Tract Infections

From WiserWiki

[edit] Urinary Tract Infections

Bahar Bastani

Urinary tract infection (UTI) is the most common bacterial infection affecting humans.Up to one third of all female patients experience at least one episode of UTI in their lives.UTIs occur in all ages, neonatal to geriatric; they have a particular impact on female patients, male patients at the two extremes of life (infancy and after 50 years of age), and anyone with functional or structural abnormalities of the urinary tract.The infection may be limited to one part of or extend throughout the urinary tract and may involve the perinephric tissues.Although the bacteriology and pathogenesis of UTI may be the same, the clinical features, the risk of acute or chronic complications, and the treatment vary depending on where the infection is and whether functional or structural abnormalities are present.

[edit] EPIDEMIOLOGY AND ETIOLOGY

[edit] Definitions and Terminologies

Despite the pitfalls and difficulties in determining bacteriologic localization, the UTIs have conventionally been classified into those involving the upper vs.the lower urinary tract.Each category is further divided into uncomplicated vs.complicated UTI, depending on the absence or presence of host conditions known to promote infection, account for persistence of infection, or promote recurrence of infection.Although the majority of the uncomplicated UTIs occur in young women and are community acquired, complicated UTIs occur in patients with anatomic or urologic abnormalities or with recent urinary catheterization or instrumentation, involve both sexes, and are often hospital acquired.The complicated UTIs are associated with a higher incidence of antimicrobial resistance, a poorer response to therapy, and a higher risk of renal damage, urosepsis, and abscess formation.^[1][2][3]

The lower UTIs include cystitis, prostatitis, and urethritis (Box 146-1).Atrophic vaginitis; sexually transmitted diseases caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex; and vaginal infections caused by Candida albicans or Trichomonas species can also present with dysuria and urinary frequency but are not considered UTIs (see Chapters 29 and 46 ).

The upper UTIs, which are much less common, include acute or chronic pyelonephritis and renal or perirenal abscess.Acute pyelonephritis is a clinical diagnosis based on the presence of fever, flank tenderness, and bacteriuria.However, the diagnosis of chronic pyelonephritis is based on radiologic demonstration of calyceal clubbing and deformity associated with renal scarring, typically a sequela of bacterial infection superimposed on an anatomic abnormality of the urinary tract (e.g., obstruction, more often vesicoureteral reflux).

The term acute urethral syndrome(also called the dysuria-pyuria syndrome) describes women with signs and symptoms suggestive of lower UTI but less than 10⁵colonies/ml of urine.Between 30% and 50% of all patients with dysuria have this condition. Asymptomatic bacteriuria refers to the presence of more than 10⁵colonies of the same bacterial species per milliliter of urine in two consecutive midstream urine cultures and in the absence of any signs or symptoms of UTI.

[edit] Incidence and Prevalence

Except during the newborn period, when the incidence of UTI in both symptomatic and asymptomatic infants is much greater in boys than in girls, in all other age groups, UTIs occur much more frequently in female patients.The incidence of UTI, which only occasionally occurs in prepubertal girls, greatly increases in late adolescence and during the third and fourth decades of life.Approximately one third of women 20 to 40 years of age develop signs and symptoms suggestive of UTI.During the reproductive years, women are 20 to 50 times more likely to acquire UTI than men.It is more common in sexually active women, and its incidence increases with age.The difference in the incidence of UTI between men and women diminishes in later life.In the older age group, hospitalization for other illnesses is frequently associated with urinary catheterization and the acquisition of nosocomial UTI.Hospitalization and catheterization increase the risk of infection in both sexes.

[edit] Uropathogenic Bacteria

Most UTIs are caused by bacteria that originate from flora in the lower gut.^[1][2][3]Escherichia coli, normally present in large quantities in the feces, accounts for 80% to 90% of uncomplicated community-based UTIs.The same strain of E.coli recovered from infected urine is usually also recovered from the patient's periurethra, vagina, and rectum.However, not all E.coli strains are uropathogenic, and a relatively small number of strains that possess certain virulence factors cause most UTIs.

Other enteric gram-negative bacteria (such as Klebsiella pneumoniae, Enterobacter aerogenes, and Proteus species) and gram-positive bacteria (such as Enterococcus faecalis and Staphylococcus saprophyticus) are also common uropathogens.However, anaerobic bacteria, which are present in much greater abundance in the gut flora, only rarely produce UTI.

Although the urethra, periurethra, introitus, and vagina do not normally contain significant quantities of the uropathogenic bacteria, in women with recurrent UTI, a heavy colonization with the uropathogenic bacteria precedes or is associated with the episodes of UTI.Table 146-1 shows the frequency of different uropathogenic bacteria in uncomplicated community-acquired and complicated hospital-associated UTIs.

Table 146-1 Prevalence of Microorganisms in Uncomplicated Outpatient vs.Complicated Hospital- associated UTIs

S.saprophyticus is the second most common pathogen isolated from young women.It accounts for 10% to 15% of uncomplicated lower UTIs, especially during summer and autumn.The bacterial counts with this organism are often less than 10⁵colonies/ml of urine.Its pathogenic role at this low titer has been supported by the finding of 10²to 10⁴colonies/ml in bladder urine obtained via suprapubic aspiration in symptomatic young women.

Among gram-negative microorganisms, Proteus mirabilis is particularly important because it produces the enzyme urease, which splits urea into carbon dioxide and ammonia.This process results in alkalinization of urine and leads to the formation of struvite stones that entrap the bacteria, protecting them from antimicrobial agents (see Chapter 147 ).The continued growth of bacteria leads to further urinary alkalinization and the precipitation of struvite crystals, resulting in the formation of massive staghorn stones.

Since the contamination of urine samples by bacteria normally present in the anterior urethra or periurethra occurs often, especially in women, a bacterial count of greater than 10⁵colonies/ml from a clean-catch midstream urine has been traditionally used to distinguish genuine bladder bacteriuria from contamination.In men, since contamination of carefully collected urine is less common, a count greater than 10⁴colonies/ml of urine with the same organism has been considered adequate for diagnosing bladder bacteriuria.However, prospective studies of women with recurrent UTI have shown that bacterial counts of less than 10⁵colonies/ml may be responsible for symptoms on some occasions.Moreover, some recent studies have demonstrated that in about one third of women with acute lower UTI caused by E.coli, S.saprophyticus, and Proteus species, there are of 10²to 10⁴colonies/ml in midstream urine.Similarly, acute pyelonephritis has been reported in association with low bacterial counts in voided urine.Thus many cases of the acute urethral syndrome are in fact bacterial UTIs with low colony counts, and they respond to the usual antibiotics.

Genuine mixed infections with a significant number of different microorganisms occur infrequently except in catheterized patients and those with ileal conduit, stones, neurogenic bladder, or vesicocolonic fistula.The presence of mixed infection is best confirmed by culture of urine samples obtained via sterile catheterization or suprapubic aspiration.

[edit] Host Susceptibility and Bacterial Virulence Factors

Several systemic and local factors increase host susceptibility for developing UTI.^[1][2][3] Malnutrition, diabetes mellitus, an altered immune system, local receptor characteristics of uroepithelial cells, the presence of foreign bodies (stone, stent, catheter), urine stasis (obstruction or neuromuscular dysfunction such as neurogenic bladder), and congenital or acquired abnormalities (ureterovesical reflux, bladder diverticula) all predispose patients to develop UTI.Other risk factors include lack of circumcision in infants and young sexually active men, insertive anal intercourse, and the use of diaphragm and spermicides by sexually active women.

Bacterial virulence factors are bacterial characteristics that facilitate infection of the urinary tract.These include bacterial adherence, capsular K antigens, endotoxins, resistance to serum bactericidal effects, hemolysin production and iron- binding proteins, and finally the ability to produce urease enzyme.

Bacterial selective adherence to genitourinary mucosal surfaces can influence the degree of colonization by rendering the organisms resistant to being washed out by the urinary flow.The presence of adhesins on the bacterial fimbriae (pili), which recognize their specific receptors in some humans' uroepithelial cells, plays the most important role in bacterial adherence and colonization leading to infection.

E.coli elaborates a capsular antigen also called K antigen. Certain K antigens, when expressed in high quantities, can determine the degree of virulence of the strain (i.e.whether the organisms can produce pyelonephritis or only cystitis).

The toxic properties of gram-negative bacteria relate to the endotoxins present in the bacterial wall calledlipopolysaccharide-containing lipid A. Lipid A is immunogenic and induces antibodies that cross-react among different gram-negative bacteria and thus decrease the frequency of shock and death in patients with gram-negative sepsis.

Many strains of gram-negative bacteria are killed in the presence of fresh human serum via a process that involves the activation of complement pathways. E.coli strains isolated from patients with acute pyelonephritis or acute cystitis have been found to be significantly more serum resistant than strains normally found in the feces.

Since bacteria require iron, their ability to release hemolysin, resulting in hemolysis of the host erythrocytes and release of hemoglobin, and their iron-binding protein content are the other two important virulence factors.

[edit] Normal Defense Mechanisms of the Urinary Tract

A variety of specific and nonspecific mechanisms protect the urinary tract against microbial invasion.One of the nonspecific resistant mechanisms is the lactobacilli of the normal vaginal and introital flora, which interfere with the adhesion and thus colonization with the uropathogenic E.coli. Another mechanism is a hydrophilic glycocalyx protein on the surface of the bladder epithelium, rendering it resistant to bacterial adherence.Moreover, Tamm-Horsfall glycoprotein in the urine binds to E.coli receptors and facilitates the removal of E.coli in the urine.Finally, the normal slow shedding of bladder epithelial cells is greatly increased during episodes of UTI, resulting in removal of a greater number of organisms from the urinary tract.

The specific immune responses in the urinary tract consist of urinary secretory immunoglobulin A (IgA), half of which originates in the urethra, providing a barrier to the ascent of bacteria, and IgG excretion, which is increased during acute pyelonephritis.

[edit] PATHOPHYSIOLOGY

[edit] Routes of Infection

Bacteria generally do not enter the urinary system by filtration.The three well-recognized routes of infection are (1) ascending infection, as with fecal microorganisms colonizing the periurethral area and subsequently entering the bladder via the urethra; (2) hematogenous spread, as in staphylococcal bacteremia and bacterial seeding of the renal cortex, resulting in abscess formation; and (3) direct extension, as with enterovesical fistula.^[1][2][3]

Ascending transurethral infection is the most common route.The short female urethra offers little obstacle to the passage of uropathogenic bacteria, which have colonized the periurethral area, to the bladder.Sexual intercourse forces bacteria into the bladder, accounting for the increased incidence of UTIs in sexually active women.In male patients, the length of the urethra, the distance between the external urethral orifice and the perianal area, and the presence of antibacterial factors in prostatic secretions are all responsible for the reduced risk of infection.The presence of a foreskin, fecal incontinence, and poor toilet habits promote colonization by the fecal bacteria and contribute to the higher prevalence of infection seen in uncircumcised infants and young, sexually active men as well as elderly men with poor anal sphincter control.Catheterization or other instrumentation in either sex increases the risk of UTI, which has been reported to occur with a frequency of 1% after an acute bladder catheterization.In patients with indwelling bladder catheters and an open drainage system, infection invariably occurs within a few days.

Hematogeneous spread of bacteria, fungi, and mycobacteria from a distant focus of infection may invade the kidneys, bladder, or prostate.Renal cortical and perirenal abscesses caused by staphylococci or group A streptococci are frequently the result of bacteremia with a primary focus of infection in another organ.

Direct extension of bacteria from the gut into the bladder may occur via a colovesical fistula secondary to diverticulitis or colon cancer or via an enterovesical fistula, as in Crohn's disease.These infections are usually recurrent, polymicrobial (high titers of several different species of enteric bacteria present), and accompanied by pneumaturia (air in the urine) or fecaluria (fecal material in the urine).

[edit] HISTORY AND PHYSICAL FINDINGS

[edit] Symptoms and Signs of Lower vs.Upper UTI^[1][2][3]

Acute bacterial cystitis produces inflammation of the bladder and urethra.The typical symptoms of uncomplicated lower UTI include dysuria, frequency, urgency, nocturia, voiding of small urine volumes, incontinence, and suprapubic or pelvic pain.Hematuria may occur and is usually at the termination of voiding; however, women may have total gross hematuria and may even pass clots.Patients may also complain of a foul-smelling or cloudy urine.Fever and flank tenderness occur infrequently in these patients.

With acute pyelonephritis, patients are generally sicker with flank or low back pain, chills, fever, sweats, nausea, vomiting, headache, and malaise.Patients often have symptoms of cystitis.Gross or microscopic hematuria is present in 10% to 15% of patients.Acute pyelonephritis may cause either a mild or a very severe illness that may include gram-negative septicemia, papillary necrosis, oliguric or anuric acute renal failure, and intrarenal or perirenal abscess formation.In 20% of these patients, bacteremia can be documented.

With complicated UTI, such as in hospitalized patients or those with indwelling catheters, the clinical manifestations can range from asymptomatic bacteriuria to a severe gram-negative sepsis with shock.Most of the catheter-associated UTIs are asymptomatic.Similarly, a high percentage of elderly patients who are institutionalized or community based without an indwelling bladder catheter may have asymptomatic bacteriuria.Complicated UTI can also present with signs and symptoms of acute cystitis or acute pyelonephritis.The hallmark of complicated UTI is the broader spectrum of microorganisms involved, which are generally more virulent and antibiotic resistant, have a lower clinical response rate to antimicrobial therapy, and tend to recur.It should be emphasized that in hospitalized patients who suddenly develop signs and symptoms of septic shock, urosepsis should be considered, even in the absence of urinary symptoms, particularly after a recent instrumentation or catheterization.Patients with complicated UTI are particularly prone to develop urosepsis, papillary necrosis, and renal or perirenal abscess.

Although clinicians usually use patients' signs and symptoms to differentiate upper from lower UTI, diagnosing the site of infection based on clinical signs can be quite inaccurate.Approximately one half of women with asymptomaticbacteriuria may have infection originating in the upper tract.Also, as many as one third of women with characteristic symptoms of uncomplicated acute cystitis may have subclinical infection of the upper urinary tract.Moreover, flank pain and tenderness with fever may be present in up to one third of patients documented to have lower UTI.

In some patients with recurrent infection, particularly the elderly, symptoms may be much less obvious, and the patient may only notice a slight change in frequency or “smelly urine” or may develop urinary incontinence or some vague abdominal pain.

Both acute and chronic bacterial prostatitis are associated with UTI.The diagnosis is often made on the basis of symptoms of dysuria; frequency; perineal, groin, or low back pain; and difficulty in urination and the finding of an enlarged, tender prostate gland.Relapsing UTI in men is highly suggestive of chronic bacterial prostatitis.

[edit] Physical Examination

With acute cystitis, about 10% of patients may have suprapubic tenderness, but there is generally no flank tenderness.

With acute pyelonephritis, the patient's temperature may rise to 104° F (40° C), the abdomen may be distended with hypotonic bowel sounds, and there is severe tenderness in the lumbar region.In bacteremic patients, signs of septic shock may be evident.

Except for women with clear-cut signs and symptoms of upper or lower UTI associated with significant pyuria and bacteriuria and a prompt response to the appropriate antimicrobial treatment, all other women need a careful pelvic examination to rule out other conditions presenting with acute dysuria and frequency or as acute pyelonephritis (see Differential Diagnosis).

In men with UTI symptoms, physical examination should include inspection and palpation of the genitals (including retraction of the foreskin in an uncircumcised man) for evidence of urethral discharge, meatal erythema, inflammation of the glans penis, penile lesions, enlarged or tender epididymis or testicle, and inguinal lymphadenopathy.A rectal examination with palpation of the prostate gland should be a standard part of the physical examination in all men with UTI symptoms.Evidence for prostate infection has been found in one half of men with relapsing UTI.In patients with acute bacterial prostatitis, the prostate gland is swollen, warm, and tender, whereas in those with chronic bacterial prostatitis, the gland is usually but not always tender and may feel slightly irregular.Massage of the prostate gland in patients with acute bacterial prostatitis may result in bacteremia and should be avoided.

[edit] Natural Course

In most women, acute cystitis is an isolated event that may never or rarely be repeated.The onset of sexual activity or change in sexual partner may coincide with the attack.In a small number of women, UTI may be recurrent, and the episodes may chronologically coincide with coitus.In many women, symptoms may disappear spontaneously as a result of high fluid intake.The response to antimicrobial agents is usually prompt.Acute symptoms disappear within 2 to 3 days.If untreated, in some patients, especially pregnant women or patients with obstruction, the infection may extend to the upper tract.Although lower UTI does not predispose the patient to kidney damage, the quality of life of the affected women can be seriously impaired.

With upper UTI, the presence or absence of complicating factors is critical in defining the natural course and renal sequelae.Uncomplicated upper UTI generally leaves no residual damage and can easily be treated with antimicrobial agents.Although severe renal infection can result in cortical scars, its long-term functional significance is not clear.The presence of complicating factors such as obstruction, particularly with diabetes, sickle cell disease or trait, or abuse of analgesics or nonsteroidal antiinflammatory drugs, can result in severe bacterial nephritis, papillary necrosis, life-threatening septicemia, and renal or perirenal abscess.

[edit] LABORATORY STUDIES AND DIAGNOSTIC PROCEDURES

A number of biochemical screening tests have been developed to detect significant bacteriuria.The most frequently used, the Griess test, depends on the bacterial reduction of nitrate normally present in the urine into nitrites, the latter being detected by a chemical reaction.Preferably, first-morning urine specimens should be used.This test is reasonably accurate in identifying Enterobacteriaceae but does not detect gram-positive organisms and Pseudomonas species.False-negative results may be caused by lack of dietary nitrate, low urine pH, ascorbic acid, or urobilinogen or may occur during diuresis, since bacteria require some time to reduce nitrate into nitrites in the bladder urine.False-positive results usually result from contamination of urine with the vaginal flora.This test and the leukocyte esterase test (detects pyuria), combined on a single inexpensive dipstick test, have greatly increased the usefulness of this approach.Bacterial counts higher than 10⁵Enterobacteriaceae/ml of urine with concomitant pyuria can be detected by this method.Overall, the combined test has a sensitivity and specificity of approximately 85% and 75%, respectively.^[3]

Microscopic examination of centrifuged urine can detect the presence of significant pyuria (greater than four white blood cells per high-power field), hematuria (greater than four red blood cells per high-power field), or both.This provides further support for the diagnosis of UTI.Although the presence of pyuria does not differentiate upper from lower UTIs, leukocyte casts strongly support the diagnosis of pyelonephritis.Documentation of pyuria is especially valuable in supporting the diagnosis of UTI in symptomatic patients who have low bacterial counts (10²to 10⁴colonies/ml of urine).Vaginitis may result in significant pyuria because of the contamination of vaginal secretions with the voided urine and should be ruled out in abacteriuric symptomatic patients who demonstrate pyuria.

Pyuria alone is not specific for bacterial infection.It can occur with nephrolithiasis, allergic interstitial nephritis, papillary necrosis, and renal tuberculosis.The persistence of pyuria after a UTI or genital infection has been eradicated requires further investigation.The presence of a significant number of squamous epithelial cells in the urine of women highly suggests that the white blood cells may be of vaginal origin.Although pyuria is present in all patients with UTI, microscopic hematuria is present in only one half of them.Pyuria in the absence of bacteriuria (sterile pyuria) should raise the possibility of renal tuberculosis or allergic interstitialnephritis.The demonstration of significant eosinophiluria would support the latter diagnosis.

Urine culture remains the “gold standard” in documenting significant bacteriuria and the presence of UTI, as well as identifying the pathogenic microorganism.To reduce the chance of contamination, clean-catch midstream urine samples should be used for culture purposes.Casual collection of urine samples often leads to heavy contamination, which makes the interpretation of microbiologic findings very difficult, if not impossible.In a few, often obese, women it may be almost impossible to obtain uncontaminated urine samples.To minimize the chance of contamination in males, the urine sample should be collected after retraction of the foreskin.To obtain a clean-catch midstream urine, the female patient with a full bladder should stand legs apart over the toilet, separate the labia with the left hand, and clean the vulva front to back with a sterile swab.The patient should then void downward into the toilet until half through without interrupting the stream, catch urine in a sterile cup, and complete voiding.In symptomatic patients with low bacterial counts in midstream urine samples, the first-morning urine sample after awakening may increase the yield, since overnight stasis of urine in the bladder allows bacteria to proliferate and be present in higher concentrations.The presence of more than one bacterium per high-power field on a Gram-stained film of uncentrifuged urine correlates with greater than 10⁵bacterial colonies/ml in 90% of patients.Approximately 50% of patients with dysuria have fewer than 10⁵bacterial colonies/ml, and in 30% the urine is sterile, leading to the diagnosis of acute urethral syndrome.^[4]

Suprapubic aspiration and bladder catheterization should be used only in patients in whom it is impossible to obtain uncontaminated urine samples or in symptomatic patients with low (10²to 10⁴colonies/ml) bacterial counts.For suprapubic aspiration of urine, the bladder should be full and percussible.This can be facilitated by the oral administration of 300 ml of fluids and 20 mg of furosemide given 1 hour before the procedure.In very obese patients, localization of the bladder by ultrasound (US) may help.With the patient in the supine position and after appropriate sterilization of the area, at the midline 1 inch above the symphysis pubis, the skin is penetrated with a 21-gauge, 4-inch-long needle.^[3]

Catheterization of the bladder should be avoided if possible, since it can introduce bacteria into the bladder, resulting in false-positive cultures as well as a 1% chance of developing a UTI.

Radiologic imaging techniques have undergone major technologic improvement in the last decade, especially in regards to the study of the genitourinary tract.Whereas the intravenous pyelogram (IVP) was formerly the gold standard, computed tomography (CT) and US are now the preferred modalities for assessing genitourinary infections.US is sensitive in detecting obstruction, perinephric and intrarenal abscesses, tumors, and cysts.Patients with pyelonephritis should have CT with contrast or US to assess the presence of foci of pyelonephritis in the renal cortex or cortical or perinephric abscesses.Although US is extremely sensitive, it is operator dependent.Thus CT with contrast may be the preferred modality in centers that do not have special competence in US.Immediately after a CT scan with contrast, it is possible to obtain the equivalent of an IVP by taking a kidney, ureter, and bladder (KUB) film in the prone position and observing the anatomic structures of the collecting system and ureters as the contrast is cleared into the bladder.^[3]

IVP is essential for visualizing the ureters, the details of calyceal anatomic structures, and the presence of stricture, calyceal dilatation, stones, or obstruction.Demonstration of calyceal details is required for an accurate diagnosis of reflux nephropathy as well as papillary necrosis.Pyelonephritis complicated by intrarenal or perinephric abscess formation is best studied by US, followed by US-guided aspiration and drainage.Coupled with appropriate antibiotic therapy, this is often a lifesaving procedure for many patients.

An US is generally indicated in patients who are hospitalized because of severe bacteremic pyelonephritis, especially if they have a slow response to intravenous antibiotic therapy.In this setting, it is imperative to rule out obstruction.In patients with septic shock caused by presumed urosepsis, an US should be performed on an emergency basis because these patients often do not respond to therapy unless obstruction, if it is the underlying pathologic problem, is relieved by a drainage procedure.In centers that do not have special competence in US, a CT with contrast may be the preferred imaging study, which similarly allows CT-guided abscess drainage.IVP is rarely indicated during an acute episode of pyelonephritis because of the poor quality of the results.Patients with clinical pyelonephritis not requiring hospitalization should have an US examination or IVP.(The IVP should be deferred at least 4 weeks to optimize its quality.) The costs of these studies are shown in Table 146-2.

Table 146-2 Comparison of the Cost of Radiologic Investigations in a University Hospital✢

✢Medicare allowable charges.

Most men with bacterial UTI have some anatomic abnormality in the urinary tract.Obstruction at the prostate level may be caused by benign hypertrophy, prostate cancer, cysts or stones in the ejaculatory ducts or vas deferens, or other prostatic problems (see Chapter 152 ).Transrectal US is the procedure of choice for imaging these pathologic conditions in the prostate and abnormalities in the bladder.New US technology permits a quantitative assessment of prostatic enlargement, detailed imaging of anatomic abnormalities, and the option to perform biopsy at the same time.An IVP may demonstrate prostatic enlargement and postvoiding residuals.It is also useful in diagnosing abnormalities in the bladder.

In women, it is generally accepted that the first episode of UTI does not require any urologic evaluation.However, the management of recurrent infection remains controversial.Multiple studies indicate a lack of cost-effectiveness of urologic studies in the evaluation of women, even those with recurrent UTIs.Therefore the routine anatomic evaluation of women with recurrent UTI cannot be strongly recommended.However, the patient's response to antimicrobial therapy may be used as a guide.Patients with relapsing infection who are cured by a 6-week course of an antibiotic and patients with recurrent reinfection who are successfully managed with a low-dose prophylactic regimen do not require anatomic evaluation.In contrast, those who fail to respond to these regimens require radiologic imaging, typically an US.Another indication for radiologic imaging is persistence of pyuria and flank pain.IVP should not be carried out during pregnancy because of the risk of irradiation to the fetus or within 6 weeks after delivery because of the pregnancy-related changes of the urinary excretory system.

When gross hematuria occurs, there is a significant risk of genitourinary cancer.US is particularly sensitive for identifying small renal cell carcinomas, especially when performed with Doppler flow analysis, which may identify tumor vascularity in the lesion.

In children with the first or second episode of UTI, particularly in those younger than 5 years of age, IVP or US as well as a voiding cystourethrogram (VCUG) should be obtained to detect obstruction or other abnormalities such as posterior urethral valve, renal scarring, or vesicoureteral reflux.^[5]

Cystoscopy is only rarely indicated.It should be reserved for the workup of older patients with gross hematuria in whom bladder cancer may be suspected.Cystoscopy may also be used in patients with recurrent or persistent unexplained urinary frequency and dysuria who have no bacteriuria on repeated testing.

[edit] DIFFERENTIAL DIAGNOSIS

Although several techniques such as ureteral catheterization, bladder washout, serum antibody response, and the antibody-coated bacteria test have been used to differentiate upper vs.lower UTI, lack of sensitivity of most of these procedures and the associated morbidity and cost have precluded their routine use in clinical practice.As mentioned earlier, the clinical signs and symptoms are not accurate for distinguishing between the two entities.Thus it is generally accepted that distinction between upper and lower UTI is better assessed by the response to treatment.Since uncomplicated UTIs do not produce kidney damage, emphasis has recently swayed from localization studies toward distinguishing between complicated and uncomplicated infections.^[1][2][3]

Between 10% and 30% of women with sexually transmitted diseases or other forms of vaginitis have frequency and dysuria.Therefore acute bacterial cystitis should be differentiated from vulvovaginitis caused by yeast, Trichomonas species, or bacterial infections, as well as sexually transmitted infections that involve the urethra and the cervix, such as those caused by C.trachomatis, N.gonorrhoeae, and herpes simplex virus.^[3]

In patients with vulvovaginitis, the discomfort on urination is generally felt externally (external dysuria) when urine flows over the inflamed labia.These patients may also complain of soreness of the vulva, malodorous vaginal discharge, pruritus, and dyspareunia.In these patients, pyuria and hematuria are very rare, and the urine culture typically reveals less than 10²colonies/ml.

Urethritis caused by sexually transmitted pathogens usually causes milder symptoms with a more gradual onset of dysuria without other urinary symptoms.These patients may also complain of vaginal discharge or bleeding (from concomitant cervicitis) or lower abdominal pain.They usually have pyuria but only rarely hematuria, and their urine culture shows less than 10²colonies/ml.The presence of gross hematuria suggests bacterial cystitis.

In postmenopausal women, atrophic changes in the mucosa of the vulvovagina and urethra caused by hormone deficiency may result in persistent or recurrent frequency and dysuria.These patients generally respond to hormone-replacement creams.Renal and other genitourinary neoplasms must also be seriously considered in differential diagnosis of the older individual who has symptoms of a UTI and hematuria for the first time.

In young, sexually active men, the uropathogenic strains of E.coli can result in an acute uncomplicated cystitis.However, some patients may develop urethral discharge and urethral leukocytosis, which mimic N.gonorrhoeae urethritis and C.trachomatis infections.

Acute pyelonephritis in a young female patient should be differentiated from other intraabdominal conditions such as pelvic inflammatory disease, appendicitis, atopic pregnancy, and ruptured ovarian cyst.

[edit] MANAGEMENT

The treatment of UTI depends on what the patient's symptoms are, whether the infection is located in the upper or lower urinary tract as judged by clinical signs and symptoms, and whether it is an isolated episode or a recurrent problem.^{[6][7][8][9][10][1][2][11][3]}

A young woman with the first episode of an acute uncomplicated cystitis does not require urinalysis or urine culture and may be treated with a short course of antibiotics on an empiric basis.No follow-up visit or culture after therapy is recommended unless symptoms persist or recur.In recent years, there has been considerable interest in the use of single-dose therapy on the basis of convenience, cost, compliance, and reduction in side effects.Trimethoprim-sulfamethoxazole (TMP-SMZ) (320/1600 mg, two double-strength tablets), amoxicillin (3 gm), cephaloridine (2 gm), gentamicin (5 mg/kg), and doxycycline (300 mg) have all been used as a single-dose regimen.In general, cure rates of 85% to 90% or even higher have been reported.Among these agents, TMP-SMZ is the preferred drug.With single-dose therapy, urinary symptoms may persist for 1 to 2 days, and a higher incidence of early recurrent infection occurs compared with a short-course treatment using the same antibiotics.

A more common practice is a short-course (3 to 5 days) treatment with either trimethoprim (100 to 200 mg every 12 hours), TMP-SMZ (one double-strength tablet, 160/800 mg every 12 hours), nitrofurantoin (100 mg every 8 or 6 hours), amoxicillin (250 mg every 8 hours), ciprofloxacin (250 to 500 mg every 12 hours), or norfloxacin (400 mg every 12 hours) (Table 146-3).Among these regimens, TMP-SMZ is considered the drug of choice because it effectively reduces the fecal, vaginal, and periurethral colonization.There has been an increasing trend in using less ampicillin, amoxicillin, and first-generation cephalosporins because there is frequent in vitro resistance and because these medications are not being very effective in the elimination of vaginal and periurethral colonization.Nitrofurantoin should not be used in patients with renal impairment because effective urinary concentrations may not be achieved and because there is an increased risk of peripheral neuropathy in these patients.Symptomatic improvement is usually obtained within 1 to 2days of therapy.The recurrence of symptoms after short-course therapy indicates the need for a urine culture and retreatment of the patient for a longer period (10 to 14 days), with the choice of antibiotic based on the urine culture results.Empiric treatment with TMP-SMZ may be instituted until the culture result is available.

Table 146-3 Cost Comparison of 3-or 10-Day Treatment Course for Uncomplicated Cystitis

✢Average wholesale price per Red Book, Montvale, NJ, 1993, Medical Economics Data Production.

Pregnant women with acute uncomplicated cystitis may be treated for 7 to 10 days with oral amoxicillin (250 mg every 8 hours), ampicillin (250 mg every 6 hours), macrocrystalline nitrofurantoin (100 mg every 6 hours), or an oral cephalosporin.

Young, healthy men with acute cystitis and no discernible complicating factor can be treated with a 7-to 10-day regimen of TMP-SMZ (one double-strength tablet, 160/800 mg every 12 hours), trimethoprim (100 to 200 mg every 12 hours), or a fluoroquinolone (norfloxacin [400 mg every 12 hours] or ciprofloxacin [250 to 500 mg every 12 hours]).A pretreatment urine culture is recommended in these patients.A urologic evaluation is usually unrewarding in those who respond to treatment.

About 20% of young women with an initial episode of acute cystitis develop recurrent infections.In patients with recurrent lower UTI, it is critical to distinguish between relapse and reinfection.

[edit] RECURRENT URINARY TRACT INFECTIONS

Relapses with the same microorganism highly suggest that the source of bacteriuria is the upper tract and are usually associated with renal stones, scars, or polycystic kidneys.A relapse would be suggested if the same microorganism is recultured and has the same antibiotic sensitivities.In men, a high chance exists that a concomitant chronic bacterial prostatitis may be responsible for these relapses.When relapse occurs despite a 2-week course of appropriate antimicrobial therapy, the treatment should be extended to 4 to 6 weeks with the hope of eradicating the microorganisms from the kidney while determining potential complicating factors such as stones, papillary necrosis, and partial obstruction with an IVP or US.

Reinfection causes more than 90% of recurrent lower UTIs in women.When one or two episodes occur per year, each acute attack should be treated with either a single dose or a short course of antibiotic therapy, as with a single infection.However, if attacks of infection are more frequent, the patient may be treated with short-course antibiotic therapy followed by a long-term (12-month), low-dose, prophylactic antibacterial regimen.

The antibiotics frequently used for low-dose prophylaxis are trimethoprim (100 mg), TMP-SMZ (half to one single-strength tablet, 40 to 80 mg/200 to 400 mg), nitrofurantoin (50 to 100 mg), norfloxacin (200 mg), and cephalexin (250 mg) taken at bedtime (Table 146-4).Trimethoprim with or without sulfamethoxazole has been a preferred regimen because it reduces the development of periurethral colonization.Side effects and the emergence of resistant strains are unusual.Patients with recurrence of infection after sexual intercourse should be encouraged to void and to use a single prophylactic dose of an antibiotic (TMP-SMZ, 80/400 mg; cephalexin, 250 mg; or nitrofurantoin, 50 to 100 mg) after each sexual intercourse.They should also be informed that the use of a diaphragm and spermicides may predispose them to recurrent UTI and that other forms of birth control are available.In general, all the patients with recurrent UTI should also be encouraged to maintain a high fluid intake and to void completely at 2-to 3-hour intervals during the day.

Table 146-4 Cost Comparison of 12 Months of Low-dose Prophylactic Antibiotic Regimen

✢Average wholesale price per Red Book, Montvale, NJ, 2000, Medical Economics Data Production.

Postmenopausal women may develop recurrent lower UTIs (reinfections), which may result from residual urine after voiding (often associated with bladder or uterine prolapse) or from lack of estrogen, which causes changes in the vaginal flora (loss of lactobacilli and increased colonization by E.coli).Prophylactic antibiotic treatment, topical estradiol cream, or hormone-replacement therapy is beneficial in these patients.

[edit] ACUTE URETHRAL SYNDROME

Patients with the acute urethral syndrome may have fewer than 10⁵colonies/ml on routine bacterial cultures.They mayhave positive isolates when viral, gonococcal, chlamydial, or other special cultures are obtained.Vaginitis and sexually transmitted diseases, including trichomoniasis, must be considered.

No obvious cause is found for the acute urethral syndrome in 10% to 30% of women with dysuria.Suggestions for management include the following: (1) wearing of cotton underwear to decrease moisture in the perineal area; (2) sitz baths followed by careful drying of the perineum; (3) weight loss and exercise; (4) urinary tract analgesia with phenazopyridine (Pyridium), 200 mg tid for 2 to 3 days (advise patient that the urine will have an orange color); and (5) referral to a urologist if symptoms persist.

[edit] ASYMPTOMATIC BACTERIURIA

Patients with asymptomatic bacteriuria with or without an indwelling catheter do not require antimicrobial treatment.^[12][8][10] The indication for treatment in these patients is the development of clinical symptoms and signs of UTI, the presence of leukopenia, renal transplantation, urea-splitting bacteria (particularly Proteus mirabilis, which can cause infection stones), the presence of some degree of upper urinary tract obstruction, pregnancy, or conditions predisposing to papillary necrosis (e.g., diabetes mellitus, sickle cell disease or trait, abuse of analgesic or nonsteroidal antiinflammatory drugs).As many as 40% of elderly men and women, especially those in nursing homes, have asymptomatic bacteriuria.However, since it only rarely leads to symptomatic infection, including pyelonephritis or sepsis, routine screening and antibiotic treatment are not advocated.Asymptomatic bacteriuria in pregnant women is an exception and should always be treated.There is an approximately 30% risk of developing acute pyelonephritis in the second or third trimester, with attendant complications for both mother and fetus (prematurity and low birth weight).Moreover, asymptomatic bacteriuria by itself has been suggested to increase the incidence of premature labor.All pregnant women should be screened for bacteriuria in the first trimester, and if it is present, they should be treated with a short course (3 to 5 days) of amoxicillin (250 mg every 8 hours), ampicillin (250 mg every 6 hours), macrocrystalline nitrofurantoin (100 mg every 6 hours), or an oral cephalosporin.After successful treatment, monthly urine cultures should be performed to detect recurrent bacteriuria.Pregnant women with recurrent asymptomatic bacteriuria can be managed safely with low-dose nitrofurantoin prophylaxis.

[edit] ACUTE PYELONEPHRITIS

Acute uncomplicated pyelonephritis can generally be treated on an outpatient basis if the patient does not have nausea or vomiting, is not severely volume depleted, has no evidence of septicemia, and is not a risk for medication nonadherence.^{[7][8][13][11]} All other patients with acute uncomplicated upper UTI, including pregnant women, should be hospitalized for an initial 2 to 3 days of parenteral therapy.A urine culture should be obtained in all patients with suspected pyelonephritis.In 20% of patients, the culture shows less than 10⁵colonies/ml of urine.A blood culture should be obtained in patients who are hospitalized.A positive blood culture is obtained in 15% to 20% of these patients.For outpatient management, a 2-week course of TMP-SMZ (160/800 mg every 12 hours), trimethoprim (200 mg every 12 hours), amoxicillin (500 mg every 8 hours), norfloxacin (400 mg every 12 hours), or ciprofloxacin (500 mg every 12 hours) is recommended.For inpatients, empiric parenteral therapy with TMP-SMZ (160/800 mg every 12 hours), ciprofloxacin (200 to 400 mg every 12 hours), gentamicin (1 mg/kg every 8 hours) with or without ampicillin (1 gm every 6 hours), or a third-generation cephalosporin (e.g., intravenous [IV] or intramuscular [IM] ceftriaxone, 1 to 2 gm daily) should be initiated until the patient becomes afebrile and there is evidence of clinical improvement, usually within 48 to 72 hours.Subsequently, the patient may be switched to oral therapy based on the sensitivity of the microorganism.Patients with uncomplicated upper UTI with or without documented bacteremia are best treated with a 2-week course of antibiotics, and in those who show evidence of relapse, a longer course (6 weeks) should be adopted.If fever and flank pain persist after 72 hours of therapy, blood and urine cultures should be repeated and US or CT of the kidneys obtained to rule out obstruction, urologic abnormalities, and renal or perirenal abscesses.A follow-up urine culture 2 weeks after the completion of antibiotic therapy is indicated.In patients with UTI complicated by stones, renal scars, diabetes, or papillary necrosis, a 6-week course of antibiotic treatment is usually necessary.However, these patients may initially be treated for only 2 weeks, and only those who show evidence of relapse may be retreated for an extended 6-week course.

All pregnant women with acute pyelonephritis should be hospitalized and initially treated with parenteral antibiotics.The choice of antibiotic may be ceftriaxone (1 to 2 gm IV or IM daily), gentamicin (1 mg/kg every 8 hours) with or without ampicillin (1 gm every 6 hours), aztreonam (1 gm every 8 to 12 hours), or TMP-SMZ (160/800 mg every 12 hours), until fever resolves.The patient should subsequently be treated with oral amoxicillin (500 mg every 8 hours), TMP-SMZ (160/800 mg every 12 hours), or a cephalosporin for 14 days.The antimicrobial therapy should be specifically targeted to the infecting microorganism as soon as the results of urine culture and antimicrobial sensitivity tests become available.Fluoroquinolones should not be used in pregnancy.TMP-SMZ is not approved for use in pregnancy, especially in the third trimester, because sulfonamides reduce the binding of bilirubin to albumin and may cause neonatal hyperbilirubinemia, but it is widely used.Gentamicin should be used with caution because of its possible toxicity to eighth-nerve development in the fetus.

In patients with symptomatic complicated upper UTI, the relatively broad array of bacterial species responsible for the infection and the severity of the patient's illness should be considered while choosing the appropriate empiric antimicrobial agents.For septicemia in hospitalized patients, IV broad-spectrum antibiotics covering Pseudomonas organisms and enterococci should be initially instituted.Ampicillin (1 gm every 6 hours) and gentamicin (1 mg/kg every 8 hours), a third-generation cephalosporin with anti-Pseudomonas activity (e.g., ceftriaxone [1 to 2 gm IV or IM daily]), aztreonam (1 gm every 8 to 12 hours), ticarcillin-clavulanate (3.2 gm every 8 hours), ciprofloxacin (400 mg every 12 hours), and imipenem-cilastatin (250 to 500 mg every 6 to 8 hours) are reasonable initial choices.After the cause of infection has been identified, antimicrobial therapy should be specifically targeted to the infecting agent.In patients who are less ill, outpatient oral therapy with ciprofloxacin or norfloxacin is appropriate.If the infecting pathogen is knownto be susceptible, TMP-SMZ is a reasonable and less costly choice.

The duration of initial therapy for complicated upper UTI is 2 to 3 weeks depending on the clinical circumstances.A follow-up urine culture should be obtained 1 to 2 weeks after the completion of therapy.With symptomatic relapse of the infection, a longer course (6 weeks) of appropriate antimicrobial therapy should be instituted.It should be emphasized that (1) complicated UTIs tend to recur unless the underlying anatomic or functional defect is corrected, (2) infections with Pseudomonas species and enterococci are more prone to recur, and (3) chronic or recurrent complicated upper UTIs result in renal damage with loss of renal function.Bacteriuria and UTI tend to recur in patients with chronic indwelling bladder catheters despite treatment of individual infections.The use of aseptic techniques, a closed catheter system, and continuous “downhill” drainage can reduce the incidence of catheter-associated UTI.Antimicrobial prophylaxis has no value for chronically catheterized patients.It has been suggested that intermittent catheterization results in lower rates of bacteriuria than a long-term indwelling catheter.Oral nitrofurantoin or TMP-SMZ prophylaxis mayreduce the incidence of bacteriuria in patients undergoing intermittent catheterization but not in those with a long-term indwelling catheter.Table 146-5 summarizes empiric therapy of different UTI syndromes.

Table 146-5 Recommended Empiric Therapy for Bacterial Urinary Tract Infections (UTIs)✢

✢Therapy should be targeted to infecting organism as soon as it is identified.

†For more details on antibiotics and their doses, see text.

[edit] REFERENCES