Lower Urinary Tract Infections

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Urinary tract infections (UTIs) are more prevalent among women than among men (ratio of 20:1), probably secondary to an anatomically short urethra and its close proximity to the vagina and rectum. It is a significant health care problem affecting an estimated 10 % to 20 % of women during their lifetimes and accounting for approximately 5.2 million office visits per year. In the past 30 years, there has been significant development in our understanding of the pathogenesis and management of urinary tract infections. The prevalence of urinary tract infections increases with age. At 1 year, 1 % to 2% of female infants demonstrate bacteriuria. After 1 year of age, the infection decreases to approximately 1 % and remains low until puberty. Between ages 15 to 24, the prevalence of bacteriuria is about 2 % to 3 % and increases to about 15 % at the age 60, 20% after age 65, and 25 % to 50 % after age 80. Sexual activity and pregnancy are major factors in younger age groups, whereas pelvic relaxation, systemic illnesses, and hospitalization play major roles in older women.

Approximately 2 % of all patients admitted to a hospital acquire a urinary tract infection, which accounts for 500,000 nosocomial infections per year. One percent of all these infections become life-threatening. Instrumentation or catheterization of the urinary tract is a precipitating factor in at least 80 % of these infections. Asymptomatic bacteriuria increases from an incidence in preschool children of 1 % to 5 % during the reproductive age groups and peaks at 10 % in the postmenopausal women.

Risk Factors For Urinary Tract Infections:

  1. Advanced age
  2. Inefficient bladder emptying
  3. Pelvic relaxation-
    • Large cystocele with high residuals
    • Uterovaginal prolapse resulting in obstructive voiding
  4. Neurogenic Bladder-
    • Diabetes Mellitus
    • Multiple Sclerosis
    • Spinal cord injuries
    • Drugs with anticholinergic effects
  5. Decreased functional ability -
    • Dementia
    • Cardiovascular accidents
    • Fecal incontinence
    • Neurologic deficits
  6. Nosocomial infections-
    • Indwelling catheters
    • Hospitalized patients
  7. Physiologic changes-
    • Decreased vaginal glycogen and increased vaginal pH in women
  8. Sexual intercourse and Diaphragm use

Definitions:
When discussing urinary tract infections, an understanding of some general definitions is essential:

Bacteriuria implies the presence of bacteria in the urine. The term includes both renal and bladder bacteriuria. Symptomatic bacteriuria can have as few as 100 CFU/ml, whereas asymptomatic bacteriuria requires the growth of 100,000 CFU/ml.

Urethritis is inflammation of the urethra and requires an adjective for modification (e.g., non-gonococcal, non-specific). In women, symptoms of urethritis are indistinguishable from those of cystitis, and pure urethritis is exceedingly rare.

Trigonitis is inflammation or localized hyperemia of the trigone part of the urinary bladder.

Cystitis indicates inflammation of the bladder and can be used as a histologic, cystoscopic, bacteriologic, or clinical term. Bacterial cystitis must be differentiated from nonbacterial cystitis (radiation or interstitial cystitis).

Pyelonephritis is a clinical term used that refers to a syndrome of chills, fever, and flank pain accompanied by bacteriuria and pyuria.

Uncomplicated is a term used to describe an afebrile infection in a patient with a structurally and functionally normal urinary tract. The majority of episodes of isolated or recurrent cystitis in women is uncomplicated and can be eradicated easily by a short course of inexpensive antibiotics.

Complicated infections are those in patients with Pyelonephritis or a urinary tract with structural or functional abnormality. These infections are often caused by bacteria that demonstrate multiple drug resistance.

Chronic as it pertains to infection, is a poorly defined term that is best avoided.

Prophylactic antimicrobial therapy is the use of antimicrobial drugs for the prevention of reinfection of the urinary tract. It assumes that bacteria have been completely eliminated before the initiation of prophylaxis.

Suppressive antimicrobial therapy refers to suppression of an existing infection that the clinician is unable to eradicate. Suppression may result in abacteriuric urine or may reduce the bacterial load without achieving sterile urine.

Reinfection describes recurrent infection with different bacteria from outside the urinary tract. This is essentially a new event, with the urine showing no growth after the preceding infection. Reinfections are often caused by the same species, such as E. coli that continue to colonize the vaginal introitus.

Relapse refers to consecutive urinary tract infections caused by the same bacterial strain from a focus within the urinary tract such as a stone.

Persistence of bacteria implies the continued presence of the same infecting microorganisms isolated at the start of treatment. This can be caused by several factors, including an underlying structural or functional abnormality, bacterial resistance, inadequate drug dosage, or poor patient compliance.

Microbiology:

Gram-negative bacilli of the family Enterobacteriaceae are responsible for 90 % of urinary tract infections. E. coli is the single most important organism and accounts for 80 % to 90 % of uncomplicated infections. Others include Klebsiella, Enterobacter, Serratia, Proteus, Psuedomonus, Providencia, and Morganella species. Pseudomonas aeruginosa infection is almost always secondary to urinary tract instrumentation. Staphylococcus epidermidis is a nosocomial pathogen identified in patients with indwelling catheters. Staphylococcus aureus is less commonly isolated and is often secondary to hematogenous renal infection. Candia albicans and other fungal organisms can cause lower urinary infections in patients with diabetes mellitus or indwelling urinary catheters. Immunocompromised patients and recipients of renal transplantation are vulnerable to candidal urinary tract infections. Viruria has been documented with many viruses, but generally in association with viremia.

The adherence of bacteria to mucosal cells appears to be a necessary step for colonization and pathogenecity. E. coli the most common and most studied pathogen has three different types of adhesins: Type 1 pilli, P-fimbriae, and X-adhesins. Bacteria posses a variety of other virulence factors, of which multidrug resistance is most clinically significant. Uropathogens develop resistance primarily through the resistance transfer plasmid.

Clinical Presentation:

The symptoms and signs of urinary tract infections in women are diverse. The most common are: dysuria, frequency, urgency, nocturia, and suprapubic discomfort. Gross hematuria is rare. Occasionally mild incontinence and hematuria may occur. Upper urinary tract infections commonly present with fever, chills, malaise, nausea and vomiting. Flank pain and costovertebral angle tenderness are usually present.

Diagnosis:

Urine Collection Methods:
To minimize contamination, women should be instructed to spread the labia, wipe the periurethral area from front to back with clean, moistened gauze sponge and collect a midstream urine sample holding labia apart. In patients with physical disabilities, sometimes it not be feasible to obtain clean catch urine, catheterization can be done.

Urine Microscopy:
A thorough microscopic examination of an uncentrifuged sample of urine can detect the presence of significant bacteria, leukocytes, and red blood cells. Pyuria is defined as more than 10 WBCs/ ml of urine. In a clinical setting with symptoms suggestive of urinary tract infection, pyuria and hematuria offer sufficient supportive evidence to warrant empiric antibiotics therapy.

Rapid Diagnostic Tests:
They are generally less accurate than urine microscopy but are convenient and cost-effective. The most common rapid detection test is the nitrate test, based on the bacterial conversion of nitrates to nitrite. Often integrated with it is the esterase test, which detects the presence of leukocyte esterase, suggesting pyuria. The test is ideally performed on first morning voided specimens to minimize false negative results.

Urine Culture:
In patients with symptoms and signs suggestive of urinary tract infection in whom no complicating factors are present, a positive urine analysis or an office rapid diagnostic test is sufficient evidence to start antibiotic therapy. A urine culture should be obtained for patients in whom diagnosis of cystitis is questionable or an upper-tract infection is suspected and for those in whom in whom complicating factors are present. Urine cultures can also be used to differentiate recurrent from persistent infection.

Traditionally bacterial growth of more than 100,000 CFU/ml was considered a positive culture. However the use of this value is limited by the fact that 20 % to 40 % of women with symptomatic urinary tract infections have lower colony counts and a single culture of 100,000 CFU/ml has a 20 % chance of representing contamination. Clinicians using commercial laboratories for urine cultures should be aware that they often report only the predominant organism in mixed cultures, and some report any culture with bacterial counts lower than 100,000 CFU/ml as negative.

Radiologic Studies:
The overwhelming majority of patients with acute cystitis do not need a full urologic workup. Radiologic studies can be useful in certain circumstances; lack of repose to appropriate antimicrobial therapy, evidence of bacterial persistence, history of calculi, potential ureteral obstruction and unexplained hematuria. When a suburethral diverticulum is suspected as the source of recurrent urinary tract infections, urethroscopy and a voiding cystourethrogram or double-balloon catheter study should be performed.

Cystourethroscopy:
Cystoscopy is helpful in older patients with cystitis to eliminate the possibility of a bladder tumor. It is also indicated in women with gross hematuria and bacterial persistence. Urethral diverticulum is not so common condition, but when suspected cystourethroscopy is very helpful. Routine use of cystourethroscopy is not recommended in patients with urinary tract infections.

Urodynamic Studies:
This is useful in patients with abnormal voiding patterns that might be the cause of recurrent infections. They can also be diagnostic in women with the possibility of a neurogenic bladder (history of pelvic or spinal surgery).

Management of Lower Urinary Tract Infection:

General measures such as rest and hydration should always be emphasized in women with urinary tract infection (UTI). Hydration dilutes urine and with frequent urination can lower bacterial counts. Acidification of urine is helpful only in recurrent infections and in patients taking methenamine compounds because the antibacterial activity of these agents is maximal at pH of 5.5 or less. Urinary analgesics such as phenazopyridine hydrochloride (Pyridium) help relieve pain and burning on urination.

General factors that influence the selection of antimicrobial agents for treatment of urinary tract infections include efficacy, cost of the agent, anticipated incidence and severity of adverse effects, and dosing interval. Ideally, the antimicrobial agent prescribed should nave minimal or no effect on fecal flora so as to minimize the risk of emergence of more pathogenic or resistant strains.

Commonly used antimicrobial agents in Urinary Tract Infections:

Drug

Oral Dosage Frequency

Minor Toxicity

Major Toxicity

Trimethoprim- sulfamethoxazole

1 tab. BID

Allergic reaction

Serious skin reactions, blood dyscrasias

Nitrofurantoin

50-100 mg q 6-8 hr.

GI upset

Peripheral neuropathy, pneumonitis

Ampicillin

250-500 mg q 6 hr.

Allergic reactions, candidal growth

Allergic reactions, pseudomembranous colitis

Tetracycline

250-500 mgq 6 hr.

GI upset, skin rash, candidal growth

Hepatic dysfunction, nephrotoxicity

Cephalexin

250-500 mgq 6 hr.

Allergic reactions

Hepatic dysfunction

Norfloxacin

400 mgq 12 hr.

Nausea, vomiting, diarrhea, abdominal pain, skin rash

Convulsions, psychoses, joint damage

Ciprofloxcin

250 mgq 12 hr

Nausea, vomiting, diarrhea, headache, rash, abdominal pain

Arrhythmias, angina, convulsions, gastrointestinal bleeding, nephritis.

For the first infections or infrequent reinfections, there is now considerable evidence that a single oral dose of an antibiotic is as effective as a conventional 7 day course therapy. Single dose therapy is cost-effective, ensures compliance, has fewer adverse effects and is less likely to cause bacterial resistance. Single dose therapy should be considered for initial treatment of acute bacterial cystitis and asymptomatic bacteriuria and for girls with cystitis who are known to have radiologically normal urinary tracts.

Recurrent Infections:

Twenty five percent of women who develop urinary tract infections have almost three infections per year, and these women make up 50% of all women presenting with acute cystitis. Once the urine has been sterilized by appropriate antimicrobial therapy, the pattern of culture-documented recurrence is helpful in the subsequent treatment of these patients. It can also be useful to identify those who require further urologic evaluation and to plan specific, predictable, appropriate therapy. Most of the patients with recurrent urinary tract infections can be treated successfully with continuous low-dose prophylaxis. Trials have shown that medication on alternate nights or even 3 nights a week is just as effective. The treatment of atrophic vaginitis should be considered in postmenopausal women with recurrent cystitis.Finally, a small percentage of patients with recurrent urinary tract infections are at high risk for serious morbidity and renal scarring from bacteriuria because of pregnancy, diabetes mellitus, congenital abnormalities, or obstructive uropathy.

Asymptomatic Bacteriuria:

It is defined as growth of more than 100,000 CFU/ml of a single bacterial species in two consecutive clean-catch urine specimens in the absence of clinical symptoms. The natural history of these infections is not completely known, but there seems to be no association with renal scarring, hypertension, or chronic renal disease. In general, treatment is not necessary. However, in certain situations (pregnancy, infections caused by Proteus species, and severe diabetes) antimicrobial therapy has proved beneficial. Treatment of asymptomatic bacteriuria in elderly women is controversial.

Prevention of Bladder Infection in Elderly Patients with Long-Term Catheterization:

10% of elderly patients with indwelling catheters develop bacteremia and gram-negative septicemia, a serious disease with significant mortality. The most important preventive measure is complete asepsis in the insertion of the catheter and in the care of patients with chronic indwelling catheters. Other helpful points are:

  • Monitor urine level in bag every 4 hours. Exchange catheter if cessation of flow for 4 hours.
  • Fluid intake of 1.5 L/day
  • Avoid catheter manipulations.
  • Exchange catheter if infection is suspected.
  • Exchange catheter every 8 to 12 weeks.

Summary:

Women are prone to urinary infections, especially before puberty and after the menopause. The main effect of infection on vesicourethral function is that 25% of the patients have uninhibited detrusor contractions with associated urethral relaxation. E. coli endotoxin causes these findings in many patients. In many patients urethral striated sphincteric spasm results, creating a vicious cycle of retention, obstructed voiding and repeated infection. The treatment is elimination of the infection by antimicrobial agents. Prevention of recurrent urinary tract infections is vital.

Suggested Reading:

  1. Melville JL, Katon W, Delaney K et al. Urinary incontinence in US women: a population-based study. Arach Intern Med 2005;165:537-542
  2. Brown JS, Vittinghoff E, Kanaya AM et al. Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol 2001;98:129-138
  3. Sandvik H, Seim A, Vanvik A et al. A severity index for epidemiological surveys of female urinary incontinence: comparison with 48-hour pad-weighing tests. Neurourol Urodyn 2000;19:137-145
  4. Jackson SL, Scholes D, Boyako EJ et al. Predictors of urinary incontinence in a prospective cohort of postmenopausal women. Obstet Gynecol 2006;108:855-862
  5. van der Vaart CH, van der Bom JG, de Leeuw JR, et al. The contribution of hysterectomy to the occurrence of urge and stress incontinence symptoms. BJOG 2002;109:149-154
  6. Moore EE, Jackson SL, Boyko EJ et al. Urinary incontinence and urinary tract infection. Obstet Gynecol 2008;111:317-323

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