Infections of the urinary tract represent a wide variety of clinical syndromes including urethritis, cystitis, prostatitis, and pyelonephritis. A urinary tract infection (UTI) is defined as the presence of microorganisms in the urine that cannot be accounted for by contamination. The organisms have the potential to invade the tissues of the urinary tract and adjacent structures.
Lower tract infections include cystitis (bladder), urethritis (urethra), prostatitis (prostate gland), and epididymitis. Upper tract infections involve the kidney and are referred to as pyelonephritis.
Uncomplicated UTIs are not associated with structural or neurologic abnormalities that may interfere with the normal flow of urine or the voiding mechanism. Complicated UTIs are the result of a predisposing lesion of the urinary tract, such as a congenital abnormality or distortion of the urinary tract, stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal flow of urine and urinary tract defenses.
Recurrent UTIs, two or more UTIs occurring within 6 months or three or more within 1 year, are characterized by multiple symptomatic episodes with asymptomatic periods occurring between these episodes. These infections are due to reinfection or to relapse. Reinfections are caused by a different organism and account for the majority of recurrent UTIs. Relapse represents the development of repeated infections caused by the same initial organism.
The most common cause of uncomplicated UTIs is E. coli, accounting for more than 80% to 90% of community-acquired infections. Additional causative organisms are Staphylococcus saprophyticus (coagulase-negative staphylococcus), Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Enterococcus spp.
The urinary pathogens in complicated or nosocomial infections may include E. coli, which accounts for less than 50% of these infections, Proteus spp., K. pneumoniae, Enterobacter spp., P. aeruginosa, staphylococci, and enterococci. Enterococci represent the second most frequently isolated organisms in hospitalized patients.
Most UTIs are caused by a single organism; however, in patients with stones, indwelling urinary catheters, or chronic renal abscesses, multiple organisms may be isolated.
Symptoms alone are unreliable for the diagnosis of bacterial UTIs. The key to the diagnosis of a UTI is the ability to demonstrate significant numbers of microorganisms present in an appropriate urine specimen to distinguish contamination from infection.
Elderly patients frequently do not experience specific urinary symptoms, but they will present with altered mental status, change in eating habits, or gastrointestinal (GI) symptoms.
A standard urinalysis should be obtained in the initial assessment of a patient. Microscopic examination of the urine should be performed by preparation of a Gram stain of unspun or centrifuged urine. The presence of at least one organism per oil-immersion field in a properly collected uncentrifuged specimen correlates with greater than 100,000 colony-forming units (CFU)/mL (105 CFU/mL) (above 108 CFU/L) of urine.
The presence of pyuria (above 10 white blood cells/mm3 [10 × 106/L]) in a symptomatic patient correlates with significant bacteriuria.
The nitrite test can be used to detect the presence of nitrate-reducing bacteria in the urine (eg, E. coli). The leukocyte esterase test is a rapid dipstick test to detect pyuria.
The most reliable method of diagnosing UTIs is by quantitative urine culture. Patients with infection usually have more than 105 bacteria/mL [108/L] of urine, although as many as one third of women with symptomatic infection have less than 105 bacteria/mL [108/L].
Treatment of urinary tract infections
The ability to eradicate bacteria from the urinary tract is directly related to the sensitivity of the organism and the achievable concentration of the antimicrobial agent in the urine. The therapeutic management of UTIs is best accomplished by first categorizing the type of infection: acute uncomplicated cystitis, symptomatic abacteriuria, asymptomatic bacteriuria, complicated UTIs, recurrent infections, or prostatitis.
These infections are predominantly caused by E. coli, and antimicrobial therapy should be directed against this organism initially. Because the causative organisms and their susceptibilities are generally known, a cost-effective approach to management is recommended that includes a urinalysis and initiation of empiric therapy without a urine culture
Short-course therapy (3-day therapy) with trimethoprim–sulfamethoxazole or a fluoroquinolone (eg, ciprofloxacin or levofloxacin, but not moxifloxacin) is superior to single-dose therapy for uncomplicated infection. Fluoroquinolones should be reserved for patients with suspected or possible pyelonephritis due to the collateral damage risk. Instead, a 3-day course of trimethoprim–sulfamethoxazole, a 5-day course of nitrofurantoin, or a one-time dose of fosfomycin should be considered as first-line therapy. In areas where there is more than 20% resistance of E. coli to trimethoprim–sulfamethoxazole, nitrofurantoin or fosfomycin should be utilized. Amoxicillin or ampicillin is not recommended because of the high incidence of resistant E. coli. Follow-up urine cultures are not necessary in patients who respond.
Complicated Urinary Tract Infections
The presentation of high-grade fever (above 38.3°C [100.9°F]) and severe flank pain should be treated as acute pyelonephritis, and aggressive management is warranted. Severely ill patients with pyelonephritis should be hospitalized and IV drugs administered initially. Milder cases may be managed with oral antibiotics in an outpatient setting. At the time of presentation, a Gram stain of the urine should be performed, along with urinalysis, culture, and sensitivities.
In the mild to moderately symptomatic patient for whom oral therapy is considered, an effective agent should be administered for 7 to 14 days, depending on the agent used. Fluoroquinolones (ciprofloxacin or levofloxacin) orally for 7 to 10 days are the first-line choice in mild to moderate pyelonephritis. Other options include trimethoprim–sulfamethoxazole for 14 days. If a Gram stain reveals gram-positive cocci, Streptococcus faecalis should be considered and treatment directed against this pathogen (ampicillin).
In the seriously ill patient, the traditional initial therapy is an IV fluoroquinolone, an aminoglycoside with or without ampicillin, or an extended-spectrum cephalosporin with or without an aminoglycoside.
If the patient has been hospitalized in the last 6 months, has a urinary catheter, or is in a nursing home, the possibility of P. aeruginosa and enterococci infection, as well as multiple-resistant organisms, should be considered. In this setting, ceftazidime, ticarcillin–clavulanic acid, piperacillin, aztreonam, meropenem, or imipenem, in combination with an aminoglycoside, is recommended. If the patient responds to initial combination therapy, the aminoglycoside may be discontinued after 3 days.
Follow-up urine cultures should be obtained 2 weeks after the completion of therapy to ensure a satisfactory response and to detect possible relapse.
Urinary tract infections in men
The conventional view is that therapy in men requires prolonged treatment. A urine culture should be obtained before treatment, because the cause of infection in men is not as predictable as in women.
If gram-negative bacteria are presumed, trimethoprim–sulfamethoxazole or a fluoroquinolone is a preferred agent. Initial therapy is for 10 to 14 days. For recurrent infections in men, cure rates are much higher with a 6-week regimen of trimethoprim– sulfamethoxazole.
Recurrent episodes of UTI (reinfections and relapses) account for a significant portion of all UTIs. These patients are most commonly women and can be divided into two groups: those with fewer than two or three episodes per year and those who develop more frequent infections.
In patients with infrequent infections (ie, fewer than three infections per year), each episode should be treated as a separately occurring infection. Short-course therapy should be used in symptomatic female patients with lower tract infection.
In patients who have frequent symptomatic infections, long-term prophylactic antimicrobial therapy may be instituted. Therapy is generally given for 6 months, with urine cultures followed periodically.
In women who experience symptomatic reinfections in association with sexual activity, voiding after intercourse may help prevent infection. Also, self-administered, single-dose prophylactic therapy with trimethoprim–sulfamethoxazole taken after intercourse significantly reduces the incidence of recurrent infection in these patients.
Women who relapse after short-course therapy should receive a 2-week course of therapy. In patients who relapse after 2 weeks, therapy should be continued for another 2 to 4 weeks. If relapse occurs after 6 weeks of treatment, urologic examination should be performed, and therapy for 6 months or even longer may be considered.
Urinary Tract Infection in Pregnancy
In patients with significant bacteriuria, symptomatic or asymptomatic treatment is recommended to avoid possible complications during the pregnancy. Therapy should consist of an agent with a relatively low adverse-effect potential (cephalexin, amoxicillin, or amoxicillin/clavulanate) administered for 7 days.
Tetracyclines should be avoided because of teratogenic effects and sulfonamides should not be administered during the third trimester because of the possible development of kernicterus and hyperbilirubinemia. Also, the fluoroquinolones should not be given because of their potential to inhibit cartilage and bone development in the newborn.
When bacteriuria occurs in the asymptomatic, short-term catheterized patient (below 30 days), the use of systemic antibiotic therapy should be withheld and the catheter removed as soon as possible. If the patient becomes symptomatic, the catheter should again be removed, and treatment as described for complicated infections should be started.
The use of prophylactic systemic antibiotics in patients with short-term catheterization reduces the incidence of infection over the first 4 to 7 days. In long-term catheterized patients, however, antibiotics only postpone the development of bacteriuria and lead to emergence of resistant organisms.