Urinary tract infection (UTI) is a common and painful human illness that, fortunately, is rapidly responsive to modern antibiotic therapy. In the preantibiotic era, UTI caused significant morbidity. Hippocrates, writing about a disease that appears to have been acute cystitis, said that the illness could last for a year before either resolving or worsening to involve the kidneys. When chemotherapeutic agents used to treat UTI were introduced in the early twentieth century, they were relatively ineffective, and persistence of infection after 3 weeks of therapy was common. Nitrofurantoin, which became available in the 1950s, was the first tolerable and effective agent for the treatment of UTI.
Since the most common manifestation of UTI is acute cystitis and since acute cystitis is far more prevalent among women than among men, most clinical research on UTI has involved women. Many studies have enrolled women from college campuses or large health maintenance organizations in the United States. Therefore, when reviewing the literature and recommendations concerning UTI, clinicians must consider whether the findings are applicable to their patient populations.
UTI may be asymptomatic (subclinical infection) or symptomatic (disease). Thus, the term UTI encompasses a variety of clinical entities, including asymptomatic bacteriuria (ABU), cystitis, prostatitis, and pyelonephritis. The distinction between symptomatic UTI and ABU has major clinical implications. Both UTI and ABU connote the presence of bacteria in the urinary tract, usually accompanied by white blood cells and inflammatory cytokines in the urine. However, ABU occurs in the absence of symptoms attributable to the bacteria in the urinary tract and does not usually require treatment, while UTI has more typically been assumed to imply symptomatic disease that warrants antimicrobial therapy. Much of the literature concerning UTI, particularly catheter-associated infection, does not differentiate between UTI and ABU. In this chapter, the term UTI denotes symptomatic disease; cystitis, symptomatic infection of the bladder; and pyelonephritis, symptomatic infection of the kidneys. Uncomplicated UTI refers to acute cystitis or pyelonephritis in nonpregnant outpatient women without anatomic abnormalities or instrumentation of the urinary tract; complicated UTI is a catch-all term that encompasses all other types of UTI. Recurrent UTI is not necessarily complicated; individual episodes can be uncomplicated and treated as such. Catheter-associated bacteriuria can be either symptomatic (CAUTI) or asymptomatic.
Epidemiology and Risk Factors
Except among infants and the elderly, UTI occurs far more commonly in females than in males. During the neonatal period, the incidence of UTI is slightly higher among males than among females because male infants more commonly have congenital urinary tract anomalies. After 50 years of age, obstruction from prostatic hypertrophy becomes common in men, and the incidence of UTI is almost as high among men as among women. Between 1 year and ~50 years of age, UTI and recurrent UTI are predominantly diseases of females. The prevalence of ABU is ~5% among women between ages 20 and 40 and may be as high as 40–50% among elderly women and men.
As many as 50–80% of women in the general population acquire at least one UTI during their lifetime—uncomplicated cystitis in most cases. Recent use of a diaphragm with spermicide, frequent sexual intercourse, and a history of UTI are independent risk factors for acute cystitis. Cystitis is temporally related to recent sexual intercourse, with a sixtyfold increase in the relative odds of acute cystitis in the 48 h after intercourse. In healthy postmenopausal women, sexual activity, diabetes mellitus, and incontinence are risk factors for UTI.
Many factors predisposing women to cystitis also increase the risk of pyelonephritis. Factors independently associated with pyelonephritis in young healthy women include frequent sexual intercourse, a new sexual partner, a UTI in the previous 12 months, a maternal history of UTI, diabetes, and incontinence. The common risk factors for cystitis and pyelonephritis are not surprising given that pyelonephritis typically arises through the ascent of bacteria from the bladder to the upper urinary tract. However, pyelonephritis can occur without clear antecedent cystitis.
About 20–30% of women who have had one episode of UTI will have recurrent episodes. Early recurrence (within 2 weeks) is usually regarded as relapse rather than reinfection and may indicate the need to evaluate the patient for a sequestered focus. Intracellular pods of infecting organisms within the bladder epithelium have been demonstrated in animal models of UTI, but the importance of this phenomenon in humans is not yet clear. The rate of recurrence ranges from 0.3 to 7.6 infections per patient per year, with an average of 2.6 infections per year. It is not uncommon for multiple recurrences to follow an initial infection, resulting in clustering of episodes. Clustering may be related temporally to the presence of a new risk factor or to the sloughing of the protective outer bladder epithelial layer in response to bacterial attachment during acute cystitis. The likelihood of a recurrence decreases with increasing time since the last infection. A case-control study of predominantly white premenopausal women with recurrent UTI identified frequent sexual intercourse, use of spermicide, a new sexual partner, a first UTI before 15 years of age, and a maternal history of UTI as independent risk factors for recurrent UTI.
The only consistently documented behavioral risk factors for recurrent UTI include frequent sexual intercourse and spermicide use. In postmenopausal women, anatomic factors affecting bladder emptying, such as cystoceles, urinary incontinence, and residual urine, are most strongly associated with recurrent UTI.
In pregnant women, ABU has clinical consequences, and both screening for and treatment of this condition are indicated. Specifically, ABU during pregnancy is associated with preterm birth and perinatal mortality for the fetus and with pyelonephritis for the mother. A Cochrane meta-analysis found that treatment of ABU in pregnant women decreased the risk of pyelonephritis by 75%.
The majority of men with UTI have a functional or anatomic abnormality of ...