Pathophysiology

Most UTIs in women are secondary to ascending infection from the periurethral or perianal area. Bacteria from the colon, vagina, or skin are the usual organisms causing the infection.¹³ Cystitis is more common in women than in men because of the short length of the urethra and the proximity of the urethral opening and vagina to the perianal area. Bacteria reach the bladder through the urethra and have the opportunity to ascend to the kidneys through the ureters.¹⁴

A relatively narrow spectrum of microorganisms cause the majority of UTIs. The most prominent pathogens are gram-negative organisms including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. E. coli represents 75% to 95% of infections in the bladder and ureters in normal genitourinary tracts. Staphylococcus saprophyticus is a species of gram-positive bacteria responsible for about 5% to 10% of uncomplicated bacterial UTIs.¹⁰ Nosocomial infections are caused by E. coli about 50% of the time; 40% of occurrences are caused by Klebsiella, Proteus, Enterobacter, Pseudomonas, and Serratia aeruginosa; 10% are caused by Enterococcus faecalis, S. saprophyticus, and Staphylococcus aureus. Pseudomonas is responsible for most UTIs found in catheterized patients.^10,13 See Table 153-1 for a tabular representation of the causes of UTI.

Most UTIs in women are not associated with complicating conditions or serious problems. Common precipitants include sexual intercourse, use of spermicidal agents, impaired voiding, recent antibiotic use, and estrogen deficiency. UTIs frequently occur in individuals with diabetes, obesity, urinary tract calculi, sickle cell trait, and frequent or indwelling bladder catheterization.⁶ In men, the reservoirs of microorganisms are not in close proximity to the urethral opening as in women; anatomic abnormalities of the urinary tract are more likely associated with UTIs in men. Risk factors associated with UTI in men include lack of circumcision, anal intercourse, HIV infection, and prostatic hypertrophy.¹⁵

Urethritis is characterized by an inflammation (mechanical, chemical, viral, or bacterial) of the urethra. Nongonococcal urethritis (NGU) is most common, with Chlamydia being the most frequent causative organism. Other urethral pathogens include Ureaplasma urealyticum, Mycoplasma hominis, herpes simplex virus (HSV), cytomegalovirus, and, in women, Trichomonas vaginalis and Gardnerella vaginalis. Noninfectious causes include Stevens-Johnson syndrome, Wegener granulomatosis, use of spermicides, and ingestion of some acidic foods.¹² Risk factors for urethritis include being a man aged 20 to 35, being a female of reproductive age, having multiple sexual partners, engaging in high-risk sexual behavior, and having a history of a sexually transmitted disease (STD).¹⁵

Children’s bladders hold a small quantity of urine compared with an adult. Constipation is a greater risk factor for UTI in children, because hard stool may further reduce the capacity of the bladder and/or restrict the flow of urine. Bacteria have a better opportunity to grow in these conditions.⁹

Risk factors for UTIs are listed in Boxes 153-1 and 153-2.

A more acute presentation, including high fever, chills, flank pain, costovertebral angle (CVA) tenderness, nausea, and vomiting, is suggestive of complicated UTI (pyelonephritis or urosepsis). A sustained bladder infection increases the risk for a complicated infection. However, kidney infection may also manifest with only bladder irritation and the absence of any of the classic signs or symptoms. Pyuria in the presence of positive urine or blood culture is indicative of a complicated UTI. Risks associated with complicated UTI include presence of urinary catheter, residual urine of 100 mL or more after voiding, obstruction in the urinary tract, azotemia resulting from kidney disease, and urinary retention.³

UTI is considered isolated with the first occurrence or a repeat occurrence at least 6 months from the previous episode. About 25% to 40% of infections are considered isolated. Unresolved infections persist when prescribed medications are not effective because of drug resistance or the presence of more than one organism with different drug sensitivities.² UTIs are considered recurrent if they occur at least three times in 1 year or twice in 6 months.⁴ There are two basic patterns of recurrence: relapse and reinfection. Relapse refers to infection caused by bacterial persistence—infection by the previously treated pathogen, which was not completely eradicated by the course of antimicrobial therapy. Reinfection refers to recurrence of infection by introduction of a new bacterial strain or regrowth of the same organism after complete eradication with treatment. Recurrent UTIs in women are usually are a result of reinfection rather than relapse, but it is difficult to determine reinfection versus relapse.¹⁶ Groups often bothered by recurrent infections are listed in Table 153-2.²

In men, symptoms of urethritis are usually mild and gradual in onset and include dysuria and irritative symptoms, frequency, urethral discharge, and pruritus at the distal end of the penis. Women may experience vaginal discharge or bleeding from concomitant cervicitis and lower abdominal pain. Urinalysis often demonstrates pyuria and less commonly, hematuria. Urine cultures generally show a colony count of less than 100/mL in urethritis.

Physical Examination

Important history to elicit from the woman with complaints of UTI symptoms includes urinary frequency, nocturia, dysuria, pruritus, fever or chills, hematuria, vaginal discomfort or discharge, pelvic discomfort, back or flank pain, date of last menstrual period, any prior history of UTIs, cervicitis, or pelvic inflammatory disease (PID). Patients should be queried about medical history, specifically immunocompromising disease or drugs, and recent instrumentation. A recent study has shown that women with a history of UTI correctly diagnose themselves (as confirmed by urine culture) as having a UTI 61% to 90% of the time.¹⁷

Vaginal symptoms, external irritation on urination, and dyspareunia are helpful in sorting out vaginal causes from those referable to the urinary tract. Male patients should be asked about urethral discharge, penile lesions, history of UTIs or sexually transmitted infections (STIs), and prior treatment. It is important to ask all patients about sexual history and risk factors for gonorrhea or chlamydia, including new or symptomatic sex partners.

The physical examination should include assessment of vital signs, signs and symptoms of acute illness, and dehydration. A careful abdominal examination including the assessment of CVA tenderness is an important aspect of the physical examination. A pelvic examination in females should be performed if there is any indication that infection is not solely associated with the urinary tract. The vulva, vagina, cervix, periurethral area, and perianal area should be assessed for discharge, excoriations, tenderness, and ulcerations. In male patients, the penis should be checked for discharge, lesions, ulcerations, and swelling. The prostate should be checked for tenderness, swelling, masses, or nodules. A rectal examination showing a tender prostate may be indicative of acute prostatitis, and a normal or enlarged prostate indicates chronic bacterial prostatitis.

The presence of cloudy urine, dysuria, and nocturia in women has shown a positive predictive value of greater than 80% for presence of UTI.¹⁸ Approximately half of women with one UTI symptom actually have the infection.⁴ Malodorous urine is not found to be indicative of infection.¹⁸ The diagnosis of UTI is suggested by the history and physical examination findings and confirmed by examination of the urine.

Diagnostics

The urinalysis is the most important initial study, with a urine dipstick as a reasonable rapid diagnostic aid. A clean-voided specimen minimizes contamination from nearby sources. Leukocyte esterase reflects the presence of white blood cells (WBCs) in the urine, but not all UTIs are associated with WBCs in the urine. Evidence-based guidelines from the University of Michigan Quality Management Program report that the presence of pyuria has a sensitivity of 80% to 90% and a specificity of 50% in predicting UTI. The nitrite test is not as good at detecting UTI; not all bacteria produce nitrate reductase, and false-positive results may occur with intake of ascorbic acid.⁵ However, in a more recent study of older women, these dipstick findings only resulted in 57% with a positive urine culture.¹⁹ In addition to leukocyte esterase and urinary nitrite, the presence of blood on the dipstick is another variable that is useful in predicting the presence of a UTI. In a study on the sensitivity and specificity of dipstick variables, the presence of nitrites was most predictive, followed by leukocytes with blood.²⁰

Urine may also be examined microscopically, which allows easier detection of red blood cells, WBCs, bacteria, and WBC casts. Correlation with subsequent culture is approximately 90%. This diagnostic is typically ordered by the provider and performed by a laboratory before culturing. Abnormalities of pH, protein, and blood are nonspecific with respect to UTIs. In the presence of symptoms but a negative dipstick result, direct demonstration by microscopy or culture should be done before the possibility of infection is excluded.

Urine culture is the definitive test; specimens should be obtained from all patients who are pregnant, are febrile, are seriously ill, have a history of frequent UTIs, live in a community with high rates of antibiotic resistance, or have recently been hospitalized, or in whom empirical treatment has failed.²¹ Cultures should be obtained in young men because these infections are unusual and suggestive of underlying problems.

The presence of multiple bacterial species identified by culture usually suggests contamination of the specimen, except in the case of catheterization or other special circumstances. Small numbers of certain pathogens, including Klebsiella organisms and E. coli, should be regarded as suspicious. Large numbers of skin flora, such as Staphylococcus epidermidis, diphtheroids, and β-hemolytic streptococci, can usually be ignored. Anaerobic bacteria do not usually cause UTIs; their presence suggests communication from the bowel. Candida organisms usually suggest vaginal contamination.

Sterile pyuria is defined as a negative urine culture despite a positive urinalysis (e.g., positive leukocyte esterase). This condition requires further investigation because the absence of pathogens on culture does not imply the absence of infection. Renal tuberculosis, systemic illness, vaginal contamination, and kidney stones can also cause leukocytosis in the absence of a positive culture. Some infectious organisms, such as those causing NGU, do not grow on standard laboratory media. Cultures specific for these organisms should be considered if the history and physical examination findings suggest a chlamydial or nongonococcal cause. However, many patients with urethral syndrome do not have a demonstrable infectious agent even when special culture media are used. Test of cure urine cultures should be obtained in men and whenever there is suspicion that an infection may not have been eradicated. Routine test of cure cultures are not indicated unless a persistent UTI is suspected. The recurrence of a UTI within 2 weeks is suggestive of a persistent UTI.²²

Renal ultrasound is useful to diagnose structural abnormalities, calculi, masses, and hydronephrosis. Persistent UTIs require more extensive urologic evaluation with referral to a urologist. Indications for ultrasound evaluation of patients with UTIs include frequent recurrent UTIs in females or failure to eradicate infection despite appropriate therapy; acute pyelonephritis in males; recurrent pyelonephritis in females; and palpable bladder or renal mass. Ultrasound is recommended for children younger than 2 years with their first febrile UTI, patients of any age with recurrent febrile UTIs, patients with a family history of kidney or urologic problems, and children with high blood pressure or retarded growth.²³

Differential Diagnosis

The differential diagnosis of an acute uncomplicated UTI includes urethritis, vaginal infections, STIs that may lead to cervicitis or PID, and other STIs that may mimic symptoms of UTI but are considered distinct from UTIs. The diagnosis is usually made on the basis of the history, presenting signs and symptoms, and findings on urinalysis and culture. In the case of a negative urine dipstick result in the presence of urinary symptoms, microscopic evaluation or culture should be performed before it is decided that a UTI is not present. The combination of cervical discharge, cervical motion tenderness, and adnexal tenderness suggests cervicitis or PID. Atrophic vaginitis should be considered in a postmenopausal woman not using topical estrogen therapy. Chlamydial and gonorrheal cultures should be obtained in sexually active individuals.

Clinical syndromes in women that mimic UTIs include acute urethral syndrome (also referred to as symptomatic abacteriuria) and interstitial cystitis. Clinical presentation is characterized by bladder irritation, frequency, urgency, and dysuria. The urinalysis is often unimpressive, with few leukocytes, no bacteria, and occasionally hematuria. Urine cultures show no significant colony counts, and urethral cultures are often negative. Symptoms of interstitial cystitis also include suprapubic discomfort, especially with a full bladder, and symptoms are often relieved with voiding. No definitive therapy for interstitial cystitis has been developed.

The differential diagnoses for chronic or recurrent UTIs include structural abnormalities (such as obstructive uropathy, congenital anomalies, urinary tract fistulas), neurologic dysfunction, renal calculi and renal masses, intrarenal and perirenal abscesses, bladder tuberculosis, and prostate enlargement in men.

Indications for urology referral include presence of macroscopic hematuria, suspected malignancy, recurrent UTIs or infections that do not respond to standard antimicrobial therapy, urinary tract anomalies or obstructions, acute scrotum, and all forms of prostatitis. Hospitalization is recommended for pregnant women with pyelonephritis.²⁴

Life Span Considerations

Asymptomatic UTIs are more prevalent in pregnant women. The U.S. Preventive Services Task Force recommends screening at the first prenatal visit or at 12 to 16 weeks’ gestation with urine culture. Prompt treatment of infection is indicated in these women to decrease the risk of acute pyelonephritis, premature delivery, and low birth weight.²¹

UTIs are the most common cause of bacterial infection in older adults but are often not accompanied by the classic signs and symptoms. Symptoms are often subtle and may include a vague change in mental status, decreased appetite, lethargy, and increased falls (sustained during efforts to get to the bathroom). UTIs are also the most common cause of sepsis, the second most common cause of bacteremia in the geriatric population, and an important cause of morbidity and mortality in nursing facilities.³⁰

Patient and Family Education

Nonpharmacologic measures have been demonstrated to prevent episodic or recurrent UTIs. Sexual intercourse and failure to void within 10 to 15 minutes after coitus are two factors most consistently associated with UTIs. In discussing the association between these two factors and UTIs with a patient, the provider must distinguish between UTIs and STIs. Drinking plenty of fluids (64 to 80 ounces daily), urinating frequently (at least every 4 hours), wiping from front to back, and using tampons during menstruation may also be helpful in preventing UTIs. Avoiding the following will help in the prevention of UTIs: using of sanitary napkins during menstruation, wiping more than once with the same tissue, extended soaking in a bathtub, wearing tight-fitting underwear made of nonbreathable fabric, and using spermicidal products. Women who have had previous UTIs should be encouraged to seek treatment as soon as symptoms are recognized.³¹

Women with recurrent UTIs should be educated about the possible benefits of antimicrobial suppression or postcoital prophylaxis, depending on the situation. Intravaginal estrogen cream may be helpful for postmenopausal women with recurrent UTIs. Patients should be informed that no reliable evidence is available showing that cranberry ingestion is associated with prevention of UTIs.³²