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MANAGEMENT OF PATIENTS WITH COMPLICATED URINARY TRACT INFECTIONS

Mariska Vanesa Cambey


0961050182
ABSTRACT
Urinary tract infection (UTI) is one of the most common pediatric infections. Urinary Tract
Infections (UTIs) occur in 1-3 % of girls and 1% of boys. In girls, the first UTI usually occurs by the
age of 5 yr, with peaks during infancy and toilet training. In boys, most UTI occur during the 1 st year of
life; UTIs are much common in uncircumcised boys, especially in the 1 st year of life. During the first
few months of life, the incidence of UTI in boys exceeds that in girls. By the end of the first year and
thereafter, first-time and recurrent UTIs are most common in girls. The incidence of UTIs varies based
on age and gender. UTIs are caused mainly by colonic bacteria, with E coli being the most frequent
pathogen, causing 75-90% of UTIs. Other common gram negative organisms include Kleibsiella,
Proteus, Enterobacter and occasionally Pseudomonas. UTIs are the most common bacterial cause of
unexplained fever in infants and young children. Signs and symptoms vary greatly by age of the
patient, becoming more specific as the child grows older. Even in the absence of specific signs, a UTI
should be included in the differential diagnosis of high grade fever. In younger children, presence of
upper respiratory infections, otitis media or gastroenteritis does not eliminate the possibility of a UTI. It
is crucial to have a clear understanding of the pathogenesis of UTI, risk factors, indications for
diagnostic tests, and the appropriate uses of antimicrobial agents in the management of children with
UTI.
A UTI is defined as colonization of a pathogen occurring anywhere along the urinary tract:
kidney, ureter, bladder, and urethra. Traditionally, UTIs have been classified by the site of infection
(pyelonephritis [kidney], cystitis [bladder], urethra [urethritis]) and by severity (complicated versus
uncomplicated). A complicated UTI describes infections in urinary tracts with structural or functional
abnormalities or the presence of foreign objects, such as an indwelling urethral catheter. Pyelonephritis
is almost always the result of bacteria migrating from the bladder to the renal parenchyma, which is
enhanced by vesicoureteral reflux. In uncomplicated pyelonephritis, the bacterial invasion and renal
damage are limited to the pyelocalyceal-medullary region; in complicated pyelonephritis, all regions of
the kidney may be affected. If the infection progresses, bacteria may invade the bloodstream, resulting
in bacteremia. Historically, UTIs have been considered a risk factor for the development of renal
insufficiency or end-stage renal disease in children. Many children receive antibiotics for fever without
a focus (such as treating a questionable otitis media) resulting in a partially treated UTI.

To established a diagnosis of complicated UTI is never a simple task, thus have a great potential
for under-diagnosis, which may lead to persistent symptoms, even progression into renal scarring or
loss of kidney function. Whereas a focused and accurate treatment in the onset of complicated UTI will
greatly improve the prognosis, especially on the long-term effect such as renal scarring. Given the
importance of proper diagnosis and treatment to improve renal function in children with complicated
UTI, this literature will be focused on the clinical manifestations, diagnosis, management and also
prevention of complicated UTI.

DEFINITION
A UTI is defined as colonization of a pathogen occurring anywhere along the urinary tract:
kidney, ureter, bladder, and urethra. Based on the site of infection its classified into upper urinary tract
infection, which is known as pyelonephritis (infection of the kidney), and lower urinary tract infection
which is cystitis (bladder infection) and infection of the urethra (urethritis). Based on the severity or the
complication its classified into uncomplicated and complicated urinary tract infections. A complicated
UTI is one that occurs because of anatomic, functional or pharmacologic factors that predispose the
patient to persistent infection, recurrent infection or treatment failure. Complicated UTIs may involve
both lower and upper tracts. Their primary significance is that they significantly increase the rate of
therapy failures. In uncomplicated pyelonephritis, the bacterial invasion and renal damage are limited
to the pyelocalyceal-medullary region; in complicated pyelonephritis, all regions of the kidney may be
affected. If the infection progresses, bacteria may invade the bloodstream, resulting in bacteremia.
EPIDEMIOLOGY
The number of true incidence in pediatric UTI is difficult to determine because there are
varying presentations that range from an absence of specific urinary complaints to fulminant urosepsis.
During the first year of life, boys have a higher incidence of UTI; in all other age groups, girls are more
prone to developing UTI. During the first year of life, the incidence of UTI in girls is 0.7% compared
with 2.7% in boys. During the first 6 months, uncircumcised boys have a 10- to 12-fold increased risk
for developing UTI. In children aged 1 to 5 years, the annual incidence of UTI is 0.9% to 1.4% for girls
and 0.1% to 0.2% for boys.
In some cases, children may present with complicated UTI secondary to a primary ureteropelvic
junction (UPJ) obstruction. More common in boys as compared to girls. Another condition that can be a
risk factors of complicated UTI are birth defects such as ureterocele and ureteral ectopia which is more
common in girls as compared to boys. Nearly 50% of children with anatomical or functional
abnormalities were detected in the first incidence of UTI.

ETIOLOGY
Although UTI may be caused by any pathogen that colonizes the urinary tract (eg, fungi,
parasites, and viruses), most causative agents are bacteria of enteric origin. The causative agent varies
based on age and associated comorbidities. E coli is the most frequent documented uropathogen.
Although antibiotic-susceptible E. coli is responsible for more than 80 percent of uncomplicated UTIs,
it accounts for fewer than one third of complicated cases. Risk factor of complicated UTI including:
Outflow obstruction

: Urethral stricture, pelviureteric junction, posterior urethral valves,


bladder neck obstruction, tumor, neuropathic bladder, cystic kidney.

Renal abnormalities

: Renal scarring, vesicoureteral reflux, renal dysplasia, duplex kidney


(duplicated collecting system)

Metabolic abnormalities

: Immunosuppression, renal failure, diabetes.

Presence of foreign objects

:Indwelling urethral catheter, stones, nephrostomy tube.

PATHOGENESIS
Complicated urinary tract infections (UTIs) occur in the setting of a urinary tract that has
metabolic, functional, or structural abnormalities. Complicated UTIs may involve both lower and upper
tracts.Their primary significance is that they significantly increase the rate of therapy failures. Due to
differences in anatomy, girls are at a higher risk of UTI than boys beyond the first year of life. In girls,
the moist periurethral and vaginal areas promote the growth of uropathogens. The shorter urethral
length increases the chance for ascending infection into the urinary tract. Once the uropathogen reaches
the bladder, it may ascend to the ureters and then to the kidneys by some undefined mechanism.
Uropathogenic strains of E coli have been recognized to release toxins that causes cellular lysis, cause
cell cycle arrest, and promote changes in cellular morphology and function. Uropathogenic strains of E
coli have a defensive mechanism that consists of a glycosylated polysaccharide capsule that interferes
with phagocytosis and complement-mediated destruction.
Neonates and infants in their first few months of life are at a higher risk for UTI. This
susceptibility has been attributed to an incompletely developed immune system. Several studies have
shown an increased frequency of UTI in uncircumcised boys during the first year of life. Boys with
foreskin have been demonstrated to harbor significantly higher concentrations of uropathogenic
microbes that potentially may ascend into the urinary tract and lead to UTI. Fecal and perineal flora are
important factors in the development of a UTI because most UTIs result from fecal-perineal-urethral
retrograde ascent of uropathogens. The flora of the colon and urogenital region is a result of native host
immunity, existing microbial ecology, and the presence of microbe-altering drugs and foods.

Anatomic abnormalities of the urinary tract predispose children to UTI because of inadequate clearance
of uropathogens. Infections associated with urinary tract malformation generally appear in children
younger than 5 years of age. It is essential to identify these abnormalities early because if uncorrected,
they may serve as a reservoir for bacterial persistence and result in recurrent UTI. Children with a
functional abnormality of the urinary tract are also at a higher risk of developing a UTI. Inability to
empty the bladder, as in the case of neurogenic bladders, frequently results in urinary retention, urinary
stasis, and suboptimal clearance of bacteria from the urinary tract.
CLINICAL MANIFESTATIONS
Children who have UTI often do not necessarily present with the characteristic sign and
symptoms seen in the adult population. There are various clinical presentations for children with UTI
based on age. Generally, sign and symptoms of complicated urinary tract infection are similar with
uncomplicated urinary tract infection. However, in complicated UTI the systemic manifestations are
more prominent, such as fever, costovertebral tenderness accompanied by high bacterial count (>
100,000 CFU/ml) with presence of pus in urine. The degree of severity in the clinical manifestations
varies from mild, moderate, to severe. Infants younger than 90 days may have vague and non specific
symptoms of illness that are difficult to interpret, such as failure to thrive, diarrhea, irritability,
vomitting, fever, asymptomatic jaundice, malodorous urine and oliguria or polyuria. A moderate to
severe symptoms can be presented as lethargy, convulsion, or sign of sepsis as hypothermia or
hyperthermia. Abdominal pain and fever were the most common presenting symptoms in children 2
and 5 years of age. After 5 years, the classic urinary tract symptoms, including dysuria, urgency,
urinary frequency, and flank pain are more common. If the infection caused by obstruction, the clinical
presentations are hypertension, palpable kidney or bladder (indicative of a dilated urinary collection
system), signs of shock, septicemia, and abdominal distention. The sign and symptoms compatible with
gastrointestinal and respiratory infections are often present in children with UTI. As a result, UTI must
be considered in all children with serious illness even there is strong evidence of infection outside the
urinary system.
Children with inadequate antimicrobial therapy during acute symptoms generally developed
into chronic. In some of the cases, infected children were asymptomatic while the other presented with
recurrent fever, malaise, under-diagnosed sign and symptoms that were localized and persistent.
Children with infections without proper and accurate antibiotic treatment might developed reinfection
that most probably leads into recurrent UTI instead of relapses.

DIAGNOSIS
History Taking
An immunocompromisedstate (e.g., long-term steroid use, oncologic processes, acquired or
inborn immunodeficiencies, sickle cell anemia, congenital heart disease) or the presence of an
indwelling medical device (e.g., ventriculoperitoneal shunts, indwelling catheters) puts a child at
increased risk of invasive bacterial infection. The child's immunization history is also important. The
pneumococcal conjugate vaccine has significantly decreased the risk of bacteremia and other invasive
pneumococcal diseases. Prior antibiotic use may mask presenting sign or symptoms of focal bacterial
infections and should be noted.
History of enuresis (bedwetting), vomitting, diarrhea, failure to thrive, idiopathic fever may
present in children with UTI. Information about bladder control, pattern of urination, and urine stream
are also important in establishing diagnosis. Signs of polyuria, polydipsia, and notable decrease in
appetite may presenting signs of chronic kidney failure, as of the presence of weak flow of urine,
palpable mass or pain in the abdomen show signs of urethral stricture or urethral valves. Presenting
manifestations in older children are commonly the classic urinary tract symptoms such as dysuria,
pollakiuria (abnormally frequent urination), and urgency. UTI must be considered in young children (2
months 2 years) with febrile or idiopathic fever (fever of unknown origin/FUO).
Physical Examination (PE)
The PE should target the abdominal and genitourinary areas. PE must be done thoroughly in
order to detect physical signs that may show the presence of UTI. Including the physical examination
that is known to commonly associated with UTI symptoms such as fever, costovertebral tenderness (or
also known as Murphy's punch sign), lower abdominal tenderness, palpable abdominal mass or
enlarged kidney, and neurological examination especially of the lower extremities. It is also essential to
evaluate skin, mucous membranes, joints, and spine for signs of systemic infection. Genitourinary
examination can be diagnostic and direct the remainder of the evaluation. It is important to ensure
patient comfort and maximum visualization (good lighting is essential). Palpate for inguinal
lymphadenopathy. Examine the external genitalia of girls for erythema, edema, excoriations, abrasions,
and bruising. In boys, inspect the penis for redness, lesions, discharge, and size of the urethral opening.
Examination of outer genitalia including inspection of urethral orifice (phimosis, synechia vulvae,
hypospadias, epispadias).

Congenital anomalies of the kidneys and urinary tract are frequently associated with
malformation of other organs (such as macrochepaly, ear anomalies, supernumerary nipples, single
umbilical artery), therefore the patient must be thoroughly examined for these stigmata.
LAB Examination
Urinalysis of fresh and non-centrifuged urine (leukocyturia > 5/LPB or dipstick positive for
leukocyte) and urine culture are the essential examination in establishing the diagnosis of UTI. The
definitive diagnosis of UTI requires the isolation of at least one uropathogen from a urine culture.
Urine, which should be obtained before the initiation of antimicrobial therapy, can be collected in
various methods (midstream clean catch specimen of urine, urethral catheterization, supra pubic
aspiration). Accurate urine culture and susceptibility information are necessary to best target and
eradicate the pathogens in complicated UTIs. These infections are usually associated with high-count
bacteriuria (greater than 100,000 CFU per mL of urine).
The most commonly used technique in young children is urethral catheterization. The
catheterized specimen is considered reliable provided that the initial portion of urine that may be
contaminated by periurethral organisms is discarded. The disadvantage of urethral catheterization is
that it is invasive and periurethral organisms maybe introduced into an otherwise sterile urinary tract.
Supra pubic aspiration is considered the gold standard for accurately identifying bacteria within the
bladder, in the other hand this method is the most technically challenging and is associated with the
lowest rate of success (23%-99%). It is recommended to use supra pubic aspiration or urethral
catheterization to establish a diagnosis of UTI in neonates and young children. A midstream clean catch
specimen may be obtained from older children and young adults.

Quantitative and qualitative urine cultures should also be used to monitor the efficacy of
treatment in chronic and recurrent infections. Cultures should be repeated three to five days after the
termination of antimicrobial therapy to ensure elimination of infection. If feasible, cultures should also
be repeated two to three days after beginning therapy to ensure the antimicrobial agent selected is
effective. Remission of clinical signs should not be used to judge efficacy of treatment, especially in
chronic or recurrent infections, since infections can persist without causing clinical signs, particularly if
bacterial numbers are temporarily reduced.
If clinical picture and urinalysis are equivocal, additional tests, such as a complete blood count,
erythrocyte sedimentation rate, and C-reactive protein, may help to determine the presence of a UTI
and whether presumptive treatment should be initiated.
Diagnostic Imaging Studies
In the acute setting of UTI, a diagnostic imaging tests are generally not indicated unless the
diagnosis of UTI is equivocal. If, however, he signs and symptoms of UTI continue to persist after 2
days despite appropriate antimicrobial therapy, then either ultrasound or CT scanning can be used to
rule out disease states that may require invasive therapy, including a renal abscess, pyonephrosis,
urinary calculi, or surgically correctable anatomic abnormalities.
Chest radiographs are indicated in children with significant respiratory symptoms or persistent
tachypnea. As the sign and symptoms compatible with respiratory infections are often present in
children with UTI.
After a diagnosis of a UTI in a young child, a further workup of urinary tract anatomy may be
indicated including test such as renal ultrasound (renal ultrasound permits diagnosis of ureteropelvic
junction obstruction), voiding cystourethrogram to visualize a person urethra and urinary bladder while
the person urinates, or dimercaptosuccinic acid (DMSA) renal scan for assessing kidney functions. It is
controversial whether the routine use of a cystourethrogram to identify vesicoureteral reflux after the
first UTI is necessary.

MANAGEMENT AND TREATMENT


A generally healthy young child with a presumed uncomplicated UTI who is non-toxic, is
taking in fluids, has reliable caretakers, and is able to follow-up on a daily basis may be managed as an
outpatient with oral antibiotics. In these patient, a broad spectrum antibiotic is recommended for
empiric coverage. First line agents include amoxicillin, trimethoprimsulfamethoxazole (TMP-SMX),
nitrofurantoin, and cephalosporins. It is important to consider the prevailing antimicrobial resistance
patterns when selecting a drug for treatment of presumed UTI.
In contrast, an acutely ill child, immunocompromised patients, or infant younger than 2 months
of age is assumed to have acute pyelonephritis or complicated UTI. Complicated UTIs are more
difficult to treat and usually requires more aggressive evaluation, treatment and follow-up. It may
require identifying and addressing the underlying complication. These patients should be managed with
hospital admission, rehydration, and parenteral broad-spectrum antimicrobial therapy immediately after
urine culture is obtained. To be noted, infants younger than 90 days are more likely to have their course
of diseases change rapidly because of their physiology and incompletely developed immune system.
Patients of any age with pyelonephritis who are vomitting, are dehydrated, have severe abdominal pain,
or are otherwise ill appearing should be hospitalized. A sepsis evaluation that includes a suprapubic
aspiration and blood cultures should be initiated upon evaluation. Any patient with questionable
compliance or difficulty with follow-up should be considered for inpatient management. In general, the
combination of ampicillin or cephalosporin, plus an aminoglycoside (e.g, gentamicin) is adequate
coverage for most uropathogens. Because of changing resistance patterns of uropathogens and a
concern for nephrotoxicity, a single third-generation cephalosporin (eg, ceftriaxone or ceftazidime) is
increasingly being used as an alternative initial regimen. The promptness of therapy for suspected acute
pyelonephritis is of paramount importance, because a delay in therapy has been associated with more
severe infections and worse renal damage. Parenteral treatment is maintained until a patient is clinically
stable and afebrile, generally 48 to 72 hours. At that point, the antimicrobial regimen may be changed
to an oral agent based on the sensitivities of the urine culture. For children aged 2 months to 2 years,
the guidelines established by the AAP (American Academy of Pediatric) suggest completion of a 7 to
14-day course. For older children, the optimal total duration of treatment remains debatable. Numerous
published studies, however, have shown resolution of symptoms and eradication of the causative agent
with a 7 to 14 days course of antibiotics.

Alternative options for ambulatory management include outpatient parenteral therapy for
patients with clinical presentations consistent with acute pyelonephritis. Several studies have
demonstrated that once-daily parenteral administration of gentamicin or ceftriaxone in a day treatment
center is safe, effective, and cost-effective in children with UTI. Once the uropathogen is isolated in the
urine culture and the antimicrobial sensitivities are finalized, children can be switched to an oral agent
to complete a 10 day treatment course. A 14 day course of oral cefixime has been shown to be an
efficacious and cost-effective therapeutic option in children with UTI who can tolerate fluids.
Intravenous and oral formulations of fluoroquinolones have been shown to have excellent coverage of
gram-negative and positive organisms in the urinary tract. Fluoroquinolones, such as ciprofloxacin,
may be considered in the management of pediatric UTI. After 7 to 14 day course initial therapy, it is
suggested to give long term treatment with prophylactic antibiotic until radiographic examination of
kidney and ureter results are obtained. Because renal damage and scarring have been shown to occur
only in the presence of infectio, the goal of prophylactic antibiotic is to sterilize the urine. If
radiographic examination shows normal result, prophylactic antibiotic can be given in 6 month course.
If the result shows any abnormalities, the prophylactic antibiotic treatment can be given in 1-2 year
course.
Antipyretics may be used for comfort. Supportive care including good oral hydration, pain
control as needed, and nasal saline/suction or treatment of respiratory symptoms may be helpful. Close
medical follow up in all children with fever is imperative.
PREVENTION
Generally the prevention of UTI can be done by seeking the children to drink fluids(most
preferably water) 8 to 10 glasses a day. Some studies recommend drinking cranberry juice, as it may
prevent the attachment of E. coli to the bladder wall. Appropriate daily requirement of Vitamin C is
recommended as it results in the acidity of urine which in turn promotes non-hostile environment for
bacteria. Bubble bath and perfumed soap are not recommend as they may cause the irritation of urethra.
For infant, it is important to change the diaper regularly to avoid a prolong contact of feces with the
genital area that may provide the bacteria to travel up to the urethra and then to the bladder. For the
girls, cleaning process after urinating should be done from the front part of the genital towards the
back. Cotton underwear is suggested as it is better in preventing the bacteria growth in the urethra
region as compared to nylon. Regular urination help to remove bacteria from the urinary tract.

Prevention of completed UTI by early detection of the abnormalities in kidney and urinary tract
is essential. Predispose factors of complicated UTI include vesicoureteral reflux, neuropathic bladder,
and obstruction of the urinary tract (posterior urethral valves, ureterocele, ureteral ectopia), might as
well be a congenital anomalies that can be detected early by the antenatal ultrasound examination. AAP
recommend examination of urinary tract abnormalities by ultrasound in children < 2 years old with
diagnosis of first UTI. A long term prophylactic anti microbial agent is given to children with urinary
tract abnormalities to prevent from relapses of infection.
ALGORITHM: EVALUATION OF UTI

SUMMARY
Infections of the urinary tract are among the most common infections in the pediatric
population. The incidence of UTIs varies based on age and gender. If not treated promptly and
appropriately, pediatric UTI may lead to significant acute morbidity and irreversible renal damage.
Completed UTI often occurs in children, especially in neonates. Children, however, have a wide variety
of clinical presentation, ranging from the asymptomatic presence of bacteria in the urine to potentially
life-threatening infection of the kidney. To established a diagnosis of complicated UTI is difficult, thus
it have a great potential for under-diagnosis that will cause persistent symptoms, even progression into
renal scarring or loss of kidney function. Whereas a focused and accurate treatment in the onset of
complicated UTI will greatly improve the prognosis. A clinicians main goals are early diagnosis,
appropriate and targeted antimicrobial therapy, identification of anatomic anomalies, and preservation
of renal function. Treatment should be based on urinalysis and urine culture. Appropriate treatment of
completed UTI is parenteral broad-spectrum antimicrobial therapy immediately after urine culture is
obtained, followed by administration of prophylactic antibiotics. Children noted to have renal scarring
after an acute episode of UTI should be followed long-term for signs of hypertension and renal
insufficiency. Completed UTI prevention can be done by early detection of kidney or urinary tract
abnormalities by antenatal ultrasound examination, radiological examination (ultrasound, VCUG) in
children <2 years old with diagnosis of first UTI.

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