URINARY TRACT INFECTIONS

SUKAMTO S M

FACTS
UTIs are the most commonly occuring bacterial infections and account for 8 million patients visit annually.

Approximately 1 in 3 females will have had a UTIs by the age 24 years.

Infections in men occur much less frequently until the age of 65 years, at which point the incidence rates in men and women are similar.

DEFINITION & CLASSIFICATION

A UTIs is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination.

Uncomplicated infections Complicated infections.

Lower tract infections (cystitis, urethritis, prostatitis, and epididymitis) Upper tract infection (pyelonephritis).

DEFINITION & CLASSIFICATION

WHAT ARE UNCOMPLICATED & COMPLICATED UTIs?

Uncomplicated infections occur in individuals who lack structural or functional abnormalities of the urinary tract that interfere with the normal flow of urine or voiding mechanism.

Complicated infections are the result of a predisposing lesion of the urinary tract, such as congenital abnormality or distortion of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal flow of urine and urinary tract defenses.

Reinfection usually happens more than 2 weeks after the last UTI and is treated as a new uncomplicated UTI.

RECURRENT UTIs
Relapse usually happens within 2 weeks of the original infection and is a relapse of the original infection either because of unsuccesful treatment of the original infection, a resistant organism or anatomical abnormalities.

EPIDEMIOLOGY
The prevalence of UTIs varies with age and gender. In newborns and infants up to 6 months of age, the prevalence of abacteriuria is approximately 1% and is more common in boys. Between the ages of 1 and 6 years, UTIs occur more frequently in females. The prevalence of abacteriuria in females and males of this age group is 7% and 2%, respectively. Trough grade school and before puberty, the prevalence of UTI is approximately 1%, with 5% of females reported to have significant bacteriuria prior to leaving high school. This percentage increases dramatically to 1% to 4% after puberty in nonpregnant females primarily as a result of sexual activity.

ETIOLOGY
The bacteria causing UTIs usually originate from bowel flora of the host. The most common cause of uncomplicated UTIs is Escherichia coli, which accounts for 85% of community-acquired infections. Additional causative organism in uncomplicated infections include Staphylococcus saprophyticus (5% to 15%), Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Enterococcus spp. (5% to 10%). Organisms isolated from individuals with complicated infections are more varied and generally are more resistant than those found in uncomplicated infections. E. coli is a frequently isolated pathogen, but it accounts for less that 50% of infections. Other frequently isolated organisms include Proteus spp., K. pneumoniae, Enterobacter spp., P. aeruginosa, staphylococci, and enterococci. Most UTIs are caused by a single organism; however, in patients with stones, indwelling urinary catheters, or chronic renal abcesses, multiple organisms may be isolated.

ROUTE OF INFECTION
In general, organisms gain entry into urinary tract via three routes:
The ascending pathway Hematogenous (descending) pathway Lymphatic pathway

THE DEVELOPMENT OF INFECTION

The size of inoculum The virulence of the microorganism The competency of the natural host defense mechanisms (the primary factor)

HOST DEFENSE MECHANISMS

Bacterial growth is further inhibited in males by the addition of prostatic secretions. The urine under normal circumstances is capable of inhibiting and killing microorganisms.

The introduction of bacteria into the bladder stimulates micturition, with increased diuresis and efficient emptying of the bladder. The epithelial cells of the bladder are coated with a urinary mucus or slime called glycosaminoglycan (as an antiadherence) (hydrophilic and strongly negatively charged). After bacteria have invaded the bladder mucosa, an inflammatory response is stimulated with the mobilization of polymorphonuclear leukocytes (PMNs) and resulting phagocytosis.

The Tamm-Horsfall protein is glycoprotein produced by the ascending limb of Henle and distal tubule that is secreted into the urine and contains mannose residues.

Other factors that possibly prevent adherence of bacteria include IgA and IgG.

Another factor is the presence of Lactobacillus in the vaginal flora and circulating estrogen levels. Spermicide use, -lactam antimicrobials use, lower estrogen levels, intercourse with a new partner, and douching can lead to decreases in lactobacilli colonization

BACTERIAL VIRULENCE FACTORS

Type 1 fimbriae P fimbriae Hemolysin (a cytotoxic protein produced by bacteria that lyses a wide range of cells, including erythrocytes, PMNs, and monocytes) Aerobactin (E. coli and other gram-negative bacteria require iron for aerobic metabolism and multiplication because it facilitates the binding and uptake of iron by E. coli)

PREDISPOSING FACTORS TO INFECTION

Obstruction of urinary tract caused by:
Prostatic hypertrophy Urethral strictures Calculi Tumors Bladder diverticula Drugs such as anticholinergic agents Neurologic malfunction associated with stroke, diabetes, spinal cord injuries, tabes dorsalis, and other neuropathies

Vesicoureteral reflux caused by:

Congenital abnormality Bladder overdistension from obstruction

Urinary catheterization; mechanical instrumentation; pregnancy; and the use of spermicides and diaphragms.

CLINICAL PRESENTATION
Clinical Presentation of Urinary Tract Infections in Adults
Signs and Symptoms Lower UTI : dysuria, urgency, frequency, nocturia, suprapubic heaviness, gross hematuria Upper UTI : flank pain, fever, nausea, vomiting, malaise Laboratory Tests Bacteriuria Pyuria (white blood cell count > 10/mm3 ) Nitrite-positive urine (with nitrite reducers) Leukocyte esterase-positive urine Antibody-coated bacteria (upper UTI)

URINE COLLECTION, CHEMISTRY, AND CULTURE

There are 3 methods for collecting urine :
Midstream clean-catch Catheterization Suprapubic bladder aspiration

Several biochemical tests have been developed for screening urine for the presence of bacteria :
A common dipstick test (to detect the presence of nitrite in the urine) Leukocyte esterase dipstick test (to detect the presence of pyuria)

Several laoratory methods are used to quantify bacteria present in the urine :
Pour-plate technique Streak-plate technique

DESIRED OUTCOME
The goals of UTI treatment are:
To prevent or to treat systemic consequences of infection To eradicate the invading organism(s) To prevent the recurrence of infection

MANAGEMENT
Initial evaluation Selection of an antibacterial agent and duration of therapy
The severity of the presenting signs and symptoms The site of infection Uncomplicated or complicated Antibiotic susceptibility Side-effect, cost, the comparative inconvenience of different therapies

Follow up evaluation

MANAGEMENT
To eradicate bacteria from the urine, there are 2 main factors:
The sensitivity of the microorganism The achievable concentrations of the antimicrobial agent in the urine

A number of nonspecific therapies have been advocated in the prevention and treatment of UTIs:
Fluid hydration Cranberry juice Lactobacillus probiotics Estrogen replacement Urinary analgesics (phenazopyridine hydrochloride)

PHARMACOLOGIC THERAPY
Ideally, the antimicrobial agent chosen should be well tolerated, well absorbed, achieve high urinary concentration, and have a spectrum of activity limited to the known or suspected pathogen(s). The therapeutic management of UTIs is best accomplished by first categorizing the type of infection:
Acute uncomplicated cystitis Symptomatic abacteriuria Asymptomatic bacteriuria Complicated UTIs (e.g. pyelonephritis) Recurrent infections Prostatitis

ACUTE UNCOMPLICATED CYSTITIS

The most common form of UTI. This infection is predominantly caused by E. coli. Other common causes include S. saprophyticus, K. pneumoniae, and Proteus mirabilis. The goal of treatment for this type of infection is to eradicate the causative organism and to reduce the incidence of recurrence caused by relapse or reinfection. Acute uncomplicated cystitis can be eradicated with much shorter courses of therapy (3 days). Three-day courses of trimethoprim-sulfamethoxazole or a fluoroquinolone (ciprofloxacin, levofloxacin, or norfloxacin) are superior to single-dose therapies. Moxifloxacin is not recommended owing to the inadequate urinary concentrations. Amoxicillin and sulfonamides are not recommended because of resistance case and lower concentration in urine because of decrease of glomerular filtration rate.

SYMPTOMATIC ABACTERIURIA
Symptomatic abacteriuria or acute urethral syndrome represents a clinical syndrome in which females present with dysuria and pyuria, but the urine culture reveals less than 105 bacteria/mL of urine. These women most likely are infected with small numbers of coliform bacteria, including E. coli, Staphylococcus spp., C. trachomatis, N. gonorrhoeae, Gardnerella vaginalis, and Ureaplasma urealyticum. Drug of choice:
Single dose of Cotrimoxazole If the patient reports recent sexual activity, therapy for C.trachomatis should be considered with administration 1 g azithromycin or doxycycline 100 mg twice daily for 7 days.

ASYMPTOMATIC BACTERIURIA
This type of UTI is defined as the finding of two consecutive urine cultures with more than 105 organisms/mL of the same organism in the absence of urinary symptoms. Most patient experiencing it are elderly, female, particularly pregnant women. The management of asymptomatic bacteriuria depends on the age of the patient and whether or not the patient is pregnant. In children, because of a greater risk of developing renal scarring and long-standing renal damage, treatment should consist of conventional courses of therapy as that for symptomatic infection.

ACUTE PYELONEPHRITIS
In contrast to patients that present with lower tract UTIs, those that present with pyelonephritis will have high-grade fever [greater than 38.3C (100.9F)] and severe flank pain. Select patients with pyelonephritis may be treated in the outpatient setting; however, patients whose infection is severe enough to cause vomiting, decreased food intake, and dehydration should be treated in an inpatient hospitalized setting. These patients will receive intravenous antibiotics at first before being switched to oral therapy.

ACUTE PYELONEPHRITIS
Patients with pyelonephritis are traditionally given 14 days of therapy; however, there are limited data showing success in treating acute uncomplicated pyelonephritis for 7 to 10 days. Gram stain and culture are important in ensuring appropriate antimicrobial coverage is selected. Women who present with mild cases of pyelonephritis (defined as lowgrade fever and a normal to slightly elevated peripheral white blood cell count, without nausea or vomiting) may be treated as outpatients. Those women who exhibit more severe signs and symptoms will need to be admitted to an acute care setting for appropriate treatment.The same holds true for antibiotic selection in these patients. Those who are treated in an outpatient setting can be treated with trimethoprim sulfamethoxazole, fluoroquinolones, or even -lactam/lactamase inhibitors, such amoxicillin-as.clavulanate. In those patients that are admitted to the hospital, antibiotic therapy is usually broader in nature, especially in patients suspected of having bacteremia or urosepsis. These patients will typically receive intravenous therapy such as a fluoroquinolone, or a -lactam plus an aminoglycoside.

Pregnant Women
7% of pregnant women have an asymptomatic bacteriuria that may progress to pyelonephritis. If untreated, asymptomatic bacteriuria can lead to prematurity, low birth weight, and stillbirth. In the majority of patients, a sulfonamide (not in the third trimester due to concerns for hyperbilirubinemia), amoxicillin, amoxicillin clavulanate, cephalexin, or nitrofurantoin are effective treatment options. Tetracyclines and fluoroquinolones should be avoided due to risk of teratogenicity and ability to inhibit cartilage and bone development, respectively.

UTIs in Men
Although UTIs in men are not always complicated by definition, due to the relative infrequency ofUTIs in men compared to women, an abnormality (structural or functional) should be suspected and therefore treated as a probable complicated infection until proven otherwise. For this reason,men should not be treated with a single dose or short course of therapy if diagnosed with a UTI. Typically these patients will receive 2 weeks of therapy and in situations of failure may be treated up to 6 weeks, particularly if a prostatic source of infection is suspected. Prostatic enlargement, as previously mentioned, is a risk factor in men.

CATHETERIZED PATIENTS
The incidence of catheter-associated infection is related to a variety of factors:
Method and duration of catheterization The catheter system The care of the system The susceptability of the patient The technique of the healthcare personnel inserting the catheter