Published: November 2013
Urinary tract infections (UTIs) are the most common nosocomial infections. They account for more than 7 million physician visits and over 1 million hospital admissions in the United States each year.1, 2 They are the most common bacterial infection in older adults and the most frequent source of bacteremia.3, 4 UTIs are second in seriousness only to respiratory infections.
The term uncomplicated urinary tract infection refers to the invasion of a structurally and functionally normal urinary tract by a nonresident infectious organism. Complicated UTI refers to the occurrence of infection in most men and in patients with an abnormal structural or functional urinary tract, or both (Box 1).
In 1995, the estimate for the United States put the direct cost of community-acquired UTIs at $659 million and indirect costs, through lost productivity, at $936 million.5-8 The UTI incidence ratio in middle-aged women to men is 30 : 1; however, during later decades of life, the ratio of infection in women to men with bacteriuria progressively decreases.9 Women are especially susceptible to cystitis for reasons that are poorly understood. One factor may be that a woman’s urethra is short, allowing bacteria quick access to the bladder. Also, a woman’s urethral opening is near sources of bacteria from the anus and vagina. For many women, sexual intercourse seems to trigger an infection, although the reasons for this linkage are unclear.10 Estimates have suggested that about one third of women will have at least one episode of UTI requiring antibiotic therapy by the time they are 24 years old, and over a lifetime 50% will have had at least one UTI.5-7 Hormonally induced changes in the vaginal flora associated with menopause are responsible for its higher prevalence in older women.11
The infection spreads to the urinary tract through an ascending route of fecal flora, from the fecal reservoir through the urethra into the bladder, particularly in patients with intermittent or indwelling catheters; hematogenous dissemination, secondary to Staphylococcus aureus bacteremia; or by direct extension from adjacent organs via the lymphatic system, as in the case of retroperitoneal abscesses or severe bowel obstruction. In women, colonization of the mucosa of the vaginal introitus is an essential step in the pathogenesis of UTIs.
|Box 1 Functional and Structural Abnormalities of the Genitourinary Tract|
|Ureteric and urethral strictures|
Some people are more likely to get UTIs than others because of host factors or urothelial mucosal adherence to the mucopolysaccharide lining.12 Any abnormality of the urinary tract that interferes with the drainage of urine (e.g., kidney stones or an enlarged prostate) sets the stage for an infection, as well as foreign bodies in the bladder, such as catheters and tubes (see Box 1). Diabetes and other immunocompromised patients are at higher risk for a UTI and its complications. Sexual intercourse10 and women’s use of a diaphragm13 have also been linked to an increased risk of cystitis. Pregnancy does not increase the risk of cystitis; however, it increases the risk of pyelonephritis if UTI occurs.
Escherichia coli is the most common infecting organism in patients with uncomplicated UTIs.14 It causes 85% of community-acquired infections and approximately 50% of nosocomial infections. Other gram-negative microorganisms causing UTIs include Proteus, Klebsiella, Citrobacter, Enterobacter, and Pseudomonas spp. Gram-positive pathogens such as Enterococcus fecalis, Staphylococcus saprophyticus, and group B streptococci can also infect the urinary tract. Anaerobic microorganisms are frequently encountered in suppurative infections of the genitourinary tract (e.g., periurethral abscess, Fournier’s gangrene).
Cystitis may be asymptomatic. However, some patients report incontinence, a general lack of well-being, or both.15 Cystitis clinically manifests as irritative voiding symptoms that include frequency, dysuria, urgency, suprapubic or lower abdominal pain, and incontinence. In men, urinary retention should be ruled out, because it is frequently associated with cystitis and possible prostatitis. The manifestations of UTIs in older adults may include confusion, lethargy, anorexia, and incontinence.
Physical examination, including a pelvic examination, should be carried out in women with lower urinary tract symptoms to exclude gynecologic, neurologic, or colorectal disorders. Physicians should also maintain a high index of suspicion for underlying sexually transmitted disease (STD). Up to 50% of women presenting to an emergency department for symptoms of cystitis were found to have positive STD cultures.16
Urine samples are collected for urinalysis in a sterile container through urethral catheterization, especially in women, or by midstream voided urine after the genital area is washed to avoid contamination. The sample is then tested for bacteriuria, pyuria, and hematuria. Indirect dipstick tests are informative but less sensitive than microscopic examination of the urine. About one third of the women who have acute symptoms of cystitis have sterile urine or some other cause for the symptom.17 Many diseases of the urinary tract produce significant pyuria without bacteriuria, including staghorn calculi, tuberculosis, and infections caused by Chlamydia and Mycoplasma spp. Microscopic hematuria is found in 40% to 60% of cystitis patients.18 Associated gross hematuria should be evaluated further by imaging studies. Cystoscopy is indicated for those patients older than 50 years or who have other risk factors for concomitant diseases, such as nephrolithiasis or transitional cell carcinoma (e.g., smoking).
Whereas empirical therapies are acceptable for uncomplicated cystitis (Box 2), culture and sensitivity testing should be performed in all other cases. It should be noted that a large percentage of women with cystitis have been found to have STDs. Additional cultures for Neisseria gonorrhea, Chlamydia, Mycoplasma hominis, and Ureaplasma ureolyticus should be considered for women with recurrent lower urinary tract symptoms.
|Box 2 Urinary Tract Infection (UTI) in Adults|
|Acute cystitis in women|
|Acute pyelonephritis in young healthy women|
|Acute cystitis in men|
|Acute pyelonephritis in men|
|UTI with pregnancy|
|UTI with gross hematuria|
|UTI associated with nephrolithiasis|
|UTI associated with neurogenic bladder|
|UTI in diabetic or immunocompromised patient|
|Recurrent UTI (>3 episodes per year)|
Radiologic studies are unnecessary for the routine evaluation of patients with cystitis; however, they may be indicated to find the cause of complicated cases, in which UTIs are associated with urinary calculi, ureteral strictures, ureteral reflux, urinary tract tumors, and urinary tract diversions. The following studies may be useful:
For the general management of cystitis, the patient is advised to drink plenty of water, which helps cleanse the urinary tract of bacteria. Cranberry juice and vitamin C (ascorbic acid) supplements inhibit the growth of some bacteria by acidifying the urine. Avoiding coffee, alcohol, and spicy foods is also useful. A heating pad and pain relief medication are helpful for pain management.
Cystitis is treated with antibacterial drugs. The choice of drug and length of treatment depend on several factors (Box 3). The sensitivity test is especially useful for selecting the most effective drug.
|Box 3 Factors Influencing Selection of Antimicrobial Agents for Treating Urinary Tract Infections|
|History of drug allergy|
|Medical history (e.g., renal impairment, liver impairment)|
|Presence of urologic abnormalities|
|Spectrum of activity|
|Route of administration|
|Type of Organism|
|Results of Gram staining|
|Results of special culture and sensitivity testing|
Patients who have symptoms of frequency, urgency, pyuria on microscopic examination, and no known functional or anatomic abnormality of the genitourinary tract may be presumed to have acute uncomplicated cystitis. Empirical therapy with a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone without pretreatment culture and sensitivity testing is usually effective. Alternative regimens such as a fluoroquinolone, an oral third-generation cephalosporin, or nitrofurantoin (7-day regimen) may have a better result. Generally, for most female patients, a 3-day course seems warranted, because this demonstrates similar efficacy when compared with 7-day therapy, and with lower side effects and cost.19 Single-dose therapy usually results in lower rates of cure and more frequent recurrences.
The most common cause of recurrent UTI in women is reinfection that may occur with varying intervals and different causative organisms. Reinfection in women does not require extensive urologic evaluation. Recurrent episodes of uncomplicated cystitis can be managed by several strategies. Behavioral therapy includes increasing fluid intake, urinating as soon as the need is felt, as well as immediately after intercourse, and changing the method of contraception (for users of a diaphragm or spermicide), because spermicidal jelly contains nonoxynol 9, which decreases vaginal lactobacillus colonization and increases bacterial adherence. Long-term antimicrobial prophylaxis,20 postcoital prophylaxes with a single-dose antibiotic,21 or short-course (1- or 2-day) antibiotics for each symptomatic episode is recommended. For postmenopausal women, the use of vaginal estrogen cream may prove an effective preventive measure.11 Patients with bacterial persistence should be evaluated thoroughly to exclude potential structural or functional abnormalities.
Prostate infections are more challenging to cure because of the altered microenvironment of the inflamed tissue, which may affect antibiotic efficacy. Therefore, men with acute bacterial prostatitis often need long-term treatment (≥30 days) with a carefully selected antibiotic. Severely ill patients need hospitalization and parenteral antimicrobial agents, such as an aminoglycoside-penicillin combination, until culture and susceptibility results provide guidance for alternative, specific antibiotic regimens. In men with urinary retention, a urethral or suprapubic catheter is necessary. Suprapubic catheterization is preferable to decrease the risk of prostatic abscesses. Mild and moderate cases respond well to fluoroquinolones or TMP-SMX, both of which have a cure rate of 60% to 90%.22 Chronic bacterial prostatitis may manifest as episodes of recurrent bacteriuria with the same organism between asymptomatic periods. Episodic treatment may be prescribed using the agents mentioned and, in select patients, may be self administered as needed. Daily suppressive therapy should be considered in men with frequent cystitis if other causes are excluded, and the culpable organism is localized to the prostate, using the Meares-Stamey technique.23
When evaluating patients with LUTS, it is important to consider gynecologic and colorectal diagnoses as well. STDs in either gender may manifest as lower urinary tract symptoms (LUTS), with or without fever. Female patients, especially those presenting with severe symptoms and pain, should be screened for pregnancy, because complications such as ectopic pregnancy or abortion should be ruled out. Chronic appendicitis and sigmoid diverticulitis may be confused with an UTI. We have encountered several patients referred for evaluation of persistent or recurrent UTI or prostatitis, in whom diverticulitis (and, even rarer, chronic appendicitis) was proven to be the cause of their symptoms.
Special cultures are needed to diagnose these infections. Antibiotic therapy should be prescribed accordingly. Longer treatment with tetracycline, doxycycline, or any drug appropriate for the treatment of Mycoplasma hominis and Ureaplasma urealyticum is recommended.24 The patient’s sexual partner must be treated simultaneously.
Catheterization for longer than 2 weeks is usually associated with bacteriuria. Prophylactic antimicrobial therapy for cystitis during short-term, indwelling, urethral catheterization is not recommended. Symptomatic UTIs in older adults should be treated. Careful consideration should be given to antimicrobial choice and meticulous monitoring of drug levels in this patient population, because the older patient is more susceptible to harmful side effects of many antimicrobial agents. Short-term antimicrobial therapy (5-7 days) is indicated only for symptomatic episodes. In patients requiring long-term urinary catheterization, suprapubic catheter placement should be considered. In men, suprapubic catheterization is associated with decreased risk of meatal erosion or prostatitis. In the short term, suprapubic catheterization may be associated with a decreased risk of bacteriuria or UTI. Unfortunately, this difference is not associated with long-term catheterization.25
Funguria is a common finding in catheterized patients. Whereas most patients are asymptomatic, interventions should include change in catheter, elimination of unnecessary antimicrobials, and glycemic control. Although amphotericin B may be used for bladder irrigations, it is less effective and more expensive than oral fluconazole therapy, although the latter is a concern in patients with hepatic vulnerability.
Removal of an indwelling catheter should be prompt; whenever possible, intermittent self catheterization should be used for patients with transient or long-term urinary retention.
Bacteriuria denotes the presence of bacteria in the urine, which may be symptomatic or asymptomatic. Treatment of asymptomatic bacteriuria is indicated for pregnant women and those requiring urologic surgery.26 Preoperative treatment reduces postoperative complications, including bacteremia.27
Although the prevalence of bacteriuria identified by screening is no higher in pregnant than nonpregnant women, the presence of asymptomatic bacteriuria in a pregnant woman should be treated promptly.28 The gravid uterus causes physiologic alterations that increase the risk of pyelonephritis. Pyelonephritis has been associated with infant prematurity, low birth weight, perinatal mortality, and high blood pressure.29 The recommended regimen is 7-day treatment with ampicillin or nitrofurantoin.
When creatinine clearance is significantly impaired, antibiotic dosage should be decreased since the renal blood flow is decreased and the perfusion of antimicrobial agents into the renal tissue and urine is impaired. Ampicillin, TMP-SMX, and fluoroquinolones are all effective for the treatment of UTIs in uremic patients.30, 31 Nitrofurantoin and tetracyclines are contraindicated for the treatment of UTIs in uremic patients.
Antimicrobial prophylaxis is recommended to ensure the sterility of urine for those who appear susceptible to developing infections. These include immunocompromised patients, patients with heart disease, people with a prosthetic heart valve, and patients who are scheduled for a procedure such as cystoscopy. Oral or vaginal estrogen administered prophylactically to postmenopausal women also reduces the incidence of cystitis.26, 31