Urinary Tract Infection

Samih Al-Hayek

Definitions

Urinary tract infection (UTI) is currently defined as the inflammatory response of the urothelium to bacterial invasion usually associated with bacteriuria and pyuria.

Bacteriuria is the presence of bacteria in the urine. This can be symptomatic or asymptomatic.

Pyuria is the presence of white blood cells (WBC) in the urine, which indicates inflammation of the urothelium. This could be due to bacterial infection or other pathology such as tumour, stones, foreign body or tuberculosis.

In 1960 Edward Kass proposed defining UTI based on the finding of at least 10⁵ bacteria colonies/ml of urine regardless of symptoms. He found that a single culture of 10⁵ cfu/ml or more had a 20% chance of representing contamination. Since then, it has been shown that about 20-40% of women with symptoms of UTI have bacterial counts of less than 10⁵ (Stamey et al., 1965). In men, counts as low as 10³ cfu/ml of a pure or predominant organism have been shown to be significant in voided urine (Lipsky et al., 1987). Where there is evidence of contamination, a carefully collected repeat specimen should be examined.

In children, confirmation of UTI is dependent on the quality of the collected specimen. Negative cultures or growth of <10⁴ cfu/ml from bag urine may be diagnostically useful. However, counts of 10⁵ cfu/ml should be confirmed by culture of a more reliable specimen. This could be either a single urethral catheter specimen or, preferably, a suprapubic aspirate (SPA). Bacteriuria usually exceeds 10⁵ cfu/ml in SPAs from children with acute UTI (Ginsburg and McCracken, 1982).

For patients with indwelling catheters, urine cultures may not reflect bladder bacteriuria because sampled organisms may have arisen from biofilms on the inner surface of the catheter.

In conclusion, when making a diagnosis of UTI, the patient’s clinical condition and symptoms should be taken into account. A count of >10⁵ cfu/ml is likely to be associated with UTI regardless of symptoms. However, lower counts of 10² cfu/ml may be potentially significant in symptomatic patients, regardless of sex. A pure isolate of between 10⁴-10⁵ cfu/ml needs to be evaluated on clinical information or confirmed by repeat culture.

Classification

The main classification of UTI is (1) complicated and (2) uncomplicated. Uncomplicated UTI occurs in healthy patients with a structurally and functionally normal urinary tract. UTIs can also be classified anatomically into lower (cystitis, urethritis, prostatitis, epididymitis or orchitis) or upper tract infection (pyelonephritis).

Complicated UTI occurs in patients with underlying anatomical or functional abnormality (Table 2.1). Complicated UTIs can take longer to eradicate and tend to recur.

Clinical manifestations

Acute uncomplicated cystitis usually occurs in young women. It is an infection of the bladder that has an abrupt onset and produces severe symptoms that are usually accompanied by pyuria and bacteriuria. Symptoms include frequency, dysuria, urgency, nocturia, haematuria and occasionally incontinence. Uncomplicated cystitis can occur in some men.

Acute urethral syndrome occurs in women with acute lower urinary tract symptoms with either a low bacterial count or without demonstrable bacteriuria or vulvovaginal infection.

Table 2.1 Conditions predisposing to complicated UTI (Johnson and Stamm, 1987)

Structural/anatomical:

Urethral stricture

Ureteric stricture

Bladder diverticulum

Fistulae

Urinary diversion

Functional:

Neurogenic bladder (incomplete emptying due to dyssynergia)

Bladder outflow obstruction (e.g. prostatic enlargement)

Vesicoureteric reflux

Foreign bodies:

Indwelling catheter

Ureteric stents (2.1)

Nephrostomy tube

Urolithiasis

Other:

Pregnancy

Diabetes mellitus

Immunosuppression

Hospital-acquired infection

Chronic renal disease

Adult polycystic disease

Renal transplantation

Malignancy

Acute pyelonephritis (pyelitis) is an inflammatory process of the kidneys and adjacent structures. Symptoms include loin or abdominal pain and fever. Symptoms of cystitis may also be present. Severity ranges from mild disease to full blown Gram-negative sepsis with a few patients developing complications such as intrarenal and perinephric abscess. Such cases often require aggressive diagnostic and therapeutic measures.

Chronic pyelonephritis (chronic interstitial nephritis, or reflux nephropathy) is the second commonest cause of end-stage renal failure. It is thought to be a result of renal damage caused by UTI in infants and children with vesicoureteric reflux (VUR), or in adults with obstructive uropathy. However, it is still unclear whether recurrent infection causes progressive kidney damage.

Perinephric abscess is an uncommon complication of UTI, affecting patients with one or more anatomical or physiological abnormalities. The abscess may be confined to the perinephric space or may extend into adjacent structures. Pyuria, with or without positive culture, is seen on examination of urine. Patients may present with swinging fever, back or loin pain, and very occasionally with loin fistula. Causative organisms are usually Gram-negative bacilli but can also be staphylococci or Candida species. Mixed infections have also been reported.

Pyonephrosis results from bacterial infection of an obstructed ureter such as with a ureteric stone. Patients usually present with symptoms of pyelonephritis but will also usually have signs of obstruction on imaging. Diagnosis is made from blood culture or pus drained from the kidney. It is a urological emergency and draining the kidney is the first line of treatment.

Renal abscesses are localized in the renal cortex and may occur as a result of Staphylococcus aureus bacteraemia but they can also happen as a complication of acute pyelonephritis caused by Gram-negative bacilli. Pyuria may be present, but urine culture is usually negative.

Urethritis is common in both male and female patients. It is often associated with UTI and occasionally with bacterial prostatitis.

Male urethritis is commonly caused by sexually transmitted diseases (STD) and is associated with urethral discharge. The main organisms responsible are: Neisseria gonorrhoeae (gonococcal urethritis), Chlamydia trachomatis and Ureaplasma urealyticum (non-gonococcal urethritis or NGU).

Female patients may present with acute urethral syndrome or urethrocystitis caused by enterobacteria, Staphylococcus saprophyticus and less commonly by C. trachomatis and N. gonorrhoeae.

Prostatitis is an inflammation of the prostate gland. Routes of infection of the prostate include ascending urethral infection, reflux of infected urine into the prostatic ducts that empty into the posterior urethra, invasion of rectal bacteria by direct extension or by lymphatic spread or by haematogenous spread.

Acute bacterial prostatitis presents as an acute, febrile illness with marked constitutional and genitourinary symptoms. Chronic bacterial prostatitis is less dramatic and
features relapsing, recurrent UTIs, caused by the organisms persisting in the prostatic secretions despite antimicrobial therapy. Chronic bacterial prostatitis is less common than non-bacterial prostatitis. Bacterial prostatitis is associated with UTI. Organisms responsible are similar to those that cause UTI.

Pathogenesis

UTI is a result of a disturbed balance between the host defence and the infective organisms (2.2). If the host defence is strong, an increased bacterial virulence is needed to cause infection; however, if the patient’s defence is weakened, bacteria with minimal virulence will be able to cause infection. Virulence is the degree of pathogenicity of the organism concerned.

2.1 A ureteric stent removed from a patient.

Host factors

Most UTIs are ascending. Women are at greater risk than men because they have a shorter urethra and this sits in close proximity to the introitus. The preputial sac of uncircumcised men may harbour urinary pathogens especially Proteus causing ascending infection.

An important protective factor is dilution from fresh uninfected ureteric urine and then voiding, which must be complete. Stasis of urine increases the risk of UTI.

Factors that predispose an individual to UTI are summarized in Table 2.2.

2.2 Host and virulence factors in UTI. HLA = human leukocyte antigen; IL = interleukin; MRHA = mannoseresistant haemagglutinin.

Many pregnant women have asymptomatic bacteriuria (about 5%). If not treated, 30% may develop into acute pyelonephritis.

Diabetic women have a higher incidence of asymptomatic bacteriuria than non-diabetic women. There is no difference in the prevalence of bacteriuria between diabetic and non-diabetic men. Bladder dysfunction as a result of diabetic neuropathy may play a part as a predisposing factor in the high prevalence of UTI. UTIs tend to be more severe in diabetics.

Bacteriuria occurs in 10-20% of catheterized patients but UTI occurs in only 2-6%. Bacteraemia develops in 1-4% of catheterized patients with UTI.This has a mortality of 13-30%. Infecting organisms may originate from the patient’s perineal flora or the hands of healthcare staff during catheterization. It might be introduced via the periurethral route along the external catheter surface, or the intraluminal route as a consequence of faulty catheter care. In patients catheterized long term (>30 days), prevalence of bacteriuria is virtually 100%, infecting strains change frequently and polymicrobial bacteriuria may be present. Treatment of asymptomatic bacteriuria has not been shown to be of any benefit in reducing complications in these catheterized patients and is likely to encourage the emergence of resistant strains (Warren et al., 1982).

Table 2.2 Risk factors for UTI