URINARY TRACT INFECTION

A.    Definition

A urinary tract infection (UTI) is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli. Although urine contains a variety of fluids, salts, and waste products, it does not usually have bacteria in it, but when bacteria get into the bladder or kidney and multiply in the urine, they may cause a UTI.

The most common type of UTI is acute cystitis often referred to as a bladder infection. An infection of the upper urinary tract or kidney is known as pyelonephritis, and is potentially more serious. Although they cause discomfort, urinary tract infections can usually be easily treated with a short course of antibiotics with no significant difference between the classes of antibiotics commonly used.

B.     Signs and symptoms

The most common symptoms of a bladder infection are burning with urination (dysuria), frequency of urination, an urge to urinate, no vaginal discharge, and no significant pain. An upper urinary tract infection or pyelonephritis may also present with flank (abdominal) pain and a fever. Healthy women have an average of 5 days of symptoms.

The symptoms of urinary tract infections may vary with age and the part of the urinary system that was affected. In young children, urinary tract infection symptoms may include diarrhea, loss of appetite, nausea and vomiting, fever, and excessive crying that cannot be resolved by typical measures. Older children on the other hand may experience abdominal pain, or incontinence. Lower urinary tract infections in adults may manifest with symptoms including hematuria (blood in the urine), inability to urinate despite the urge, and malaise.

Other signs of urinary tract infections include foul-smelling urine and urine that appears cloudy.

Depending on the site of infection, urinary tract infections may cause different symptoms. Urethritis, meaning only the urethra has been affected, does not usually cause any other symptoms besides dysuria. However, if the bladder is affected (cystitis), the patient is likely to experience more symptoms, including lower abdomen discomfort, low-grade fever, pelvic pressure, and frequent urination, all together with dysuria.

Whereas in infants the condition may cause jaundice and hypothermia, in the elderly, symptoms of urinary tract infections may include lethargy and a change in mental status, signs that are otherwise nonspecific.

C.     Risk Factors

1.      Intercourse

In young sexually active women, sex is the cause of 75–90% of bladder infections, with the risk of infection related to the frequency of sex. The term "honeymoon cystitis" has been applied to this phenomenon of frequent UTI during early marriage. In post-menopausal women, sexual activity does not affect the risk of developing a UTI. Spermicide use, independent of sexual frequency, increases the risk of UTI.

2.      Gender

Women are more prone to UTIs than men because, in females, the urethra is much closer to the anus and is shorter than in males; furthermore, women lack the bacteriostatic properties of prostatic secretions. Among the elderly, UTI frequency is roughly equal in women and men. This is due, in part, to an enlarged prostate in older men. As the gland grows, it obstructs the urethra, leading to increased frequency of urinary retention.

3.      Urinary catheters

Urinary catheterization is a risk factor for urinary tract infections. The risk of an associated infection can be decreased by catheterizing only when necessary, using aseptic technique for insertion, and maintaining unobstructed closed drainage of the catheter. Infections can also be reduced by reducing the number of medically unnecessary catheters placed each year. In 2009, nearly 9.8m indwelling catheters were placed in hospitals with up to 38% considered medically unnecessary. Utilizing alternatives to indwelling catheters such as external collection devices, may significantly reduce catheter associated urinary tract infection (CAUTI).

4.      Others

A predisposition for bladder infections may run in families. Other risk factors include diabetes. While ascending infections are, in general, the rule for lower urinary tract infections, the same is not necessarily true for upper urinary tract infections like pyelonephritis, which may originate from a blood-borne infection.

D.    Pathogenesis

The most common organism implicated in UTI (80–85%) is E. coli, while Staphylococcus saprophyticus is the cause in 5–10%. The bladder wall, in common with most epithelia is coated with a variety of cationic antimicrobial peptides such as the defensins and cathelicidin which disrupt the integrity of bacterial cell walls. In addition, there are also mannosylated proteins present, such as Tamm-Horsfall proteins (THP), which interfere with the binding of bacteria to the uroepithelium. As binding is an important factor in establishing pathogenicity for these organisms, its disruption results in reduced capacity for invasion of the tissues. Moreover, the unbound bacteria are more easily removed when voiding. The use of urinary catheters (or other physical trauma) may physically disturb this protective lining, thereby allowing bacteria to invade the exposed epithelium.

During cystitis, uropathogenic Escherichia coli (UPEC) subvert innate defenses by invading superficial umbrella cells and rapidly increasing in numbers to form intracellular bacterial communities (IBCs). By working together, bacteria in biofilms build themselves into structures that are more firmly anchored in infected cells and are more resistant to immune-system assaults and antibiotic treatments. This is often the cause of chronic urinary tract infections.

E.     Prevention

The following are measures that studies suggest may reduce the incidence of urinary tract infections.

1.      A prolonged course (six months to a year) of low-dose antibiotics (usually nitrofurantoin or TMP/SMX) is effective in reducing the frequency of UTI in those with recurrent UTI.

2.      Cranberry (juice or capsules) may decrease the incidence of UTI in those with frequent infections. Long-term tolerance, however, is an issue. Subsequent research has questioned these findings.

3.      For post-menopausal women intravaginal application of topical estrogens was found to greatly reduce or prevent recurrent cystitis. As opposed to topical creams, the use of vaginal estrogen pessaries was not as useful as low dose antibiotics. E. coli continues to evolve multi-drug resistance, which bears on the evaluation of appropriate empiric therapy.

4.      Studies have shown that breastfeeding can reduce the risk of UTIs in infants.

A number of measures have not been confirmed to affect UTI frequency including: the use of birth control pills or condoms, voiding after sex, the type of underwear used, personal hygiene methods used after voiding or defecating, and whether one takes a bath instead of a shower.

F.      Diagnosis

In straight-forward cases, a diagnosis may be made and treatment given based on symptoms alone without further laboratory confirmation. In complicated or questionable cases, it may be useful to confirm via urinalysis, looking for the presence of nitrites, leukocytes, or leukocyte esterase, or via urine microscopy, looking for the presence of red blood cells, white blood cells, and bacteria (with presence of bacteria termed bacteriuria).

Urine culture showing a quantitative count of greater than or equal to 10³ colony-forming units (CFU) per mL of a typical urinary tract organism along with antibiotic sensitives is useful to guide antibiotic choice. However, women with negative cultures may still improve with antibiotic treatment.

Most cases of lower urinary tract infections in females are benign and do not need exhaustive laboratory work-ups. However, UTI in young infants may receive some imaging study, typically a retrograde urethrogram, to ascertain the presence/absence of congenital urinary tract anomalies.

Differential diagnosis

If the urine culture is negative:

1. Symptoms of urethritis may point at Chlamydia trachomatis or Neisseria gonorrheae infection.
2. Symptoms of cystitis may point at interstitial cystitis.
3. In men, prostatitis may present with dysuria.

The presence of bacteria in the urinary tract of older adults, without symptoms or signs of infection, is a well-recognized phenomenon that may not require antibiotics. This is usually referred to as asymptomatic bacteriuria. The overuse of antibiotics in the context of bacteriuria among the elderly is an issue of concern.

G.    Treatment

1.   Uncomplicated

Uncomplicated UTIs can be diagnosed and treated based on symptoms alone. Oral antibiotics such as trimethoprim, cephalosporins, nitrofurantoin, or a fluoroquinolone substantially shorten the time to recovery. All are equally effective for both short and long term cure rates. About 50% of people will recover without treatment within a few days or weeks. The Infectious Diseases Society of America recommends a combination of trimethoprim and sulfamethoxazole as a first-line agent in uncomplicated UTIs rather than fluoroquinolones. Fluoroquinolones are not recommended first line due to their cost and concern that over use will increase resistance and thus decrease the utility of this class for those with severe infections. Resistance has developed in the community to all of these medications due to their widespread use.

A three-day treatment with trimethoprim, TMP/SMX, or a fluoroquinolone is usually sufficient, whereas nitrofurantoin requires 7 days. Trimethoprim is often recommended to be taken at night to ensure maximal urinary concentrations to increase its effectiveness. While trimethoprim/sulfamethoxazole was previously internationally used (and continues to be used in the U.S. and Canada), the addition of the sulfonamide gives little additional benefit compared to the trimethoprim component alone. However, it is responsible for a high incidence of mild allergic reactions and rare but potentially serious complications. For simple UTIs, children often respond well to a three-day course of antibiotics.

2.   Pyelonephritis

A urinary tract infection that has reached the kidney (pyelonephritis) is treated more aggressively than a simple bladder infection using either a longer course of oral antibiotics or intravenous antibiotics. Regimens vary, and include SMX/TMP and fluoroquinolones. In the past, they have included aminoglycosides (such as gentamicin) used in combination with a beta-lactam (such as ampicillin or ceftriaxone). These are continued for 48 hours after fever subsides.

If there is a poor response to IV antibiotics (marked by persistent fever, worsening renal function), then imaging is indicated to rule out formation of an abscess either within or around the kidney, or the presence of an obstructing lesion such as a kidney stone or tumor.

3.   Recurrent

Women with recurrent simple UTIs may benefit from self-treatment upon occurrence of symptoms with medical follow-up only if the initial treatment fails.^[4] Effective treatment can also be delivered over the phone.

H.    Epidemiology

Bladder infections are most common in young women, with 10% of women getting an infection yearly and 60% having an infection at some point in their life.^[4] Pyelonephritis occurs between 18–29 times less frequently. Nearly 1 in 3 women will have had at least 1 episode of urinary tract infections requiring antimicrobial therapy by the age of 24 years.

The prevalence of urinary tract infections in pre-school and school girls is 1% to 3%, nearly 30-fold higher than that in boys. Approximately 5% of girls will develop at least one urinary tract infection during their school years.

Bacteriuria appears to increase in prevalence with age in women, still being 50 times greater than the one in males. It is estimated that bacteriuria will be experienced by 20 to 50% of older women and 5 to 20% of older men. In non-institutionalized elderly populations, urinary tract infections are the second-most-common form of infection, accounting for nearly 25% of all infections. The condition rarely occurs in men who are younger than 50 years old and who did not undergo any genitourinary procedure. However, the incidence of urinary tract infections in men tends to rise after the age of 50.

According to a 1997 survey, urinary tract infection accounted for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations in the United States.

I.       In Pregnancy

Urinary tract infections are more concerning in pregnancy. If urine testing shows signs of infection even in the absence of symptoms (known as asymptomatic bacteriuria) women are treated. Treatment is typically with cephalexin or nitrofurantoin as while there are no adequate studies of these antibiotics in pregnant women, many women have safely used them during pregnancy. On the other hand, research has shown that pregnancy does not increase risk of asymptomatic bacteriuria. However, if the bacteriuria is not properly treated, it can significantly increase the risk of kidney infection in pregnant women. Pregnancy makes a woman particularly vulnerable to these infections. A pregnant woman may have high levels of progesterone in the blood, which decreases the muscle tone of the ureters and bladder. This leads to a greater likelihood of reflux, where urine flows back up the ureters and towards the kidneys. In addition, the growing uterus may compress the ureters, making it harder for urine to flow through. This, coupled with the urine reflux, gives bacteria more time to replicate and may aid in infecting the kidneys. Furthermore, during pregnancy the urine may become less acidic and may contain glucose, two factors that can increase the risk of bacterial growth and increase a woman’s risk for a UTI and kidney infection.