Acquisition and etiology

Bacterial infection is usually acquired by the ascending route from the urethra to the bladder

The infection may then proceed to the kidney. Occasionally, bacteria infecting the urinary tract invade the bloodstream to cause septicaemia. Less commonly, infection may result from haematogenous spread of an organism to the kidney, with the renal tissue being the first part of the tract to be infected.

From an epidemiological viewpoint, UTIs occur in two general settings: community-acquired and hospital (nosocomially)-acquired, the latter most often being associated with catheterization. Hospital-acquired UTIs, while less common than community acquired, contribute significantly (ca. 40%) to overall nosocomial infection rates.

The Gram-negative rod Escherichia coli is the commonest cause of ascending UTI

Other members of the Enterobacteriaceae are also implicated (Fig. 20.1). Proteus mirabilis is often associated with urinary stones (calculi), probably because this organism produces a potent urease, which acts on urea to produce ammonia, rendering the urine alkaline. Citrobacter, Klebsiella, Enterobacter, Proteus, and Pseudomonas aeruginosa are more frequently found in hospital-acquired UTI because their resistance to antibiotics favours their selection in hospital patients (see Ch. 36).

Figure 20.1 Common causes of urinary tract infection. The percentages of infections caused by different bacteria in outpatients and hospital inpatients are shown. E. coli is by far the commonest isolate in both groups of patients, but note the difference in the percentage of infections caused by other Gram-negative rods. These isolates often carry multiple antibiotic resistance and colonize patients in hospital, especially those receiving antibiotics.

Among the Gram-positive species, Staphylococcus saprophyticus has a particular propensity for causing infections, especially in young sexually active women. Staphylococcus epidermidis and Enterococcus species are more often associated with UTI in hospitalized patients (especially those with AIDS), where multiple antibiotic resistance can cause treatment difficulties. In some instances, capnophilic species (organisms that grow better in air enriched with carbon dioxide), including corynebacteria and lactobacilli, have been implicated as possible causes of UTI. Obligate anaerobes are very rarely involved.

When there has been haematogenous spread to the urinary tract, other species may be found, e.g. Salmonella typhi, Staphylococcus aureus and Mycobacterium tuberculosis (renal tuberculosis).

Viral causes of UTI appear to be rare, although there are associations with haemorrhagic cystitis and other renal syndromes

Certain viruses may be recovered from the urine in the absence of urinary tract disease and include:

• The human polyomaviruses, JC and BK, enter the body via the respiratory tract, spread through the body and infect epithelial cells in the kidney tubules and ureter, where they establish latency with persistence of the viral genome. About 35% of kidneys from healthy individuals contain polyomavirus DNA sequences. However, during normal pregnancy, the viruses may reactivate asymptomatically, with the appearance of large amounts of virus in the urine. Reactivation also occurs in immunocompromised patients (see Ch. 30) and may lead to haemorrhagic cystitis.

• High titres of cytomegalovirus (CMV) and rubella may be shed asymptomatically in the urine of congenitally infected infants (see Ch. 23).

• In contrast to asymptomatic shedding, some serotypes of adenovirus have been implicated as a cause of haemorrhagic cystitis.

• The rodent-borne hantavirus responsible for Korean haemorrhagic fever infects capillary blood vessels in the kidney and can cause a renal syndrome with proteinuria.

• Finally, a number of other viruses can infect the kidneys, including mumps and HIV.

Urine samples are commonly investigated by virus isolation, immunological and genomic detection methods.

Very few parasites cause UTIs

Other causes of UTI include:

• The fungi Candida spp. and Histoplasma capsulatum.

• The protozoan Trichomonas vaginalis (see Ch. 21), which can cause urethritis in both males and females, but is most often considered as a cause of vaginitis.

• Infections with Schistosoma haematobium (see Ch. 27), which result in inflammation of the bladder and commonly haematuria. The eggs penetrate the bladder wall, and in severe infections large granulomatous reactions can occur and the eggs may become calcified. Bladder cancer is associated with chronic infections, although the mechanism is uncertain. Obstruction of the ureter as a result of egg-induced inflammatory changes can also lead to hydronephrosis.

Pathogenesis

A variety of mechanical factors predispose to UTI

Anything that disrupts normal urine flow or complete emptying of the bladder or facilitates access of organisms to the bladder will predispose an individual to infection (Fig. 20.2). The shorter female urethra is a less effective deterrent to infection than the male urethra (see Ch. 13). Sexual intercourse facilitates the movement of organisms up the urethra, particularly in females, so the incidence of UTI is higher among sexually active women than among celibate women. Preceding bacterial colonization of the periurethral area of the vagina is perhaps important (see below).

Figure 20.2 Bacterial attributes and host factors favouring urinary tract infection (UTI). Abnormalities of the urinary tract tend to predispose to infection. Bacterial adherence factors have been studied in detail, but relatively little is known about other bacterial virulence factors in UTI.

In male infants, UTIs are more common in the uncircumcised, and this is associated with colonization of the inside of the prepuce and urethra with faecal organisms.

Pregnancy, prostatic hypertrophy, renal calculi, tumours and strictures are the main causes of obstruction to complete bladder emptying

Increased volumes of post-void residual urine are associated with a greater likelihood of infection. Infection, superimposed on urinary tract obstruction, may lead to ascent of infection to the kidney and rapid destruction of renal tissue.

Loss of neurologic control of the bladder and sphincters (e.g. in spina bifida, paraplegia or multiple sclerosis), and the resultant large residual volume of urine in the bladder, causes a functional obstruction to urine flow, and such patients are particularly prone to recurrent infections.

Vesicoureteral reflux (reflux of urine from the bladder cavity up the ureters, sometimes into the renal pelvis or parenchyma) is common in children with anatomic abnormalities of the urinary tract and may predispose to ascending infection and kidney damage. Reflux may also occur in association with infection in children without underlying abnormalities, but tends to disappear with age.

Clinical studies including reports that pyelonephritis (infection of the kidney) is commonly found in people with diabetes mellitus at post-mortem suggest an increased propensity for UTI in individuals with diabetes mellitus. People with diabetes mellitus may have more severe UTIs, and if diabetic neuropathy interferes with normal bladder function, persistent UTIs are common.

Catheterization is a major predisposing factor for UTI

During insertion of the catheter, bacteria may be carried directly into the bladder and, while in situ, the catheter facilitates bacterial access to the bladder either via the lumen of the catheter or by tracking up between the outside of the catheter and the urethral wall (Fig. 20.3). The catheter disrupts the normal bladder’s protective function action and allows bacteria to get a foothold. Thus, duration of catheterization is directly associated with increased probability of infection (i.e. risk of UTI increases by about 3–10% each day of catheterization).

Figure 20.3 The urinary catheter. Catheterization is an important predisposing factor for infection. Bacteria can be pushed into the bladder as the catheter is inserted and, while the catheter is in place, bacteria reach the bladder by tracking up between the outside of the catheter and the urethra. Contamination of the catheter drainage system by bacteria from other sources can also result in infection. Specimens of bladder urine for laboratory investigations can be collected from catheterized patients as shown. The second port (above) is for putting fluids into the bladder. Urine from the drainage bag should not be tested because it may have been standing for several hours.

A variety of virulence factors are present in the causative organisms

The conflict between host and parasite in the urinary tract has been discussed in Chapter 13. Most urinary tract pathogens originate in the faecal flora, but only the aerobic and facultative species such as E. coli possess the attributes required to colonize and infect the urinary tract. The ability to cause infection of the urinary tract is limited to certain serogroups of E. coli such as O (semantic) serotypes (e.g. O1, O2, O4, O6, O7 and O75) and K (capsular) serotypes (e.g. K1, K2, K3, K5, K12 and K13). These serotypes differ from those associated with gastrointestinal tract infection (see Ch. 22), which has led to use of the term ‘uropathogenic E. coli’ (UPEC). The success of these strains is attributable to a variety of genes in chromosomal pathogenicity islands (see Ch. 2) which are not found in faecal E. coli. For example, UPEC typically contains genes associated with colonization of the periurethral areas. A prime example is the adhesion known as P. fimbriae (pyelonephritis-associated pili (PAP)), which allows UPEC to specifically adhere to urethral and bladder epithelium. Studies with other species of urinary tract pathogens have confirmed the presence of similar adhesins for uroepithelial cells (Fig. 20.4).