eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Urinary Tract Infection

Stanley Hellerstein, MD, Pediatric Nephrologist, Children's Mercy Hospital of Kansas City; Ernest L Glasscock, MD Chair in Pediatric Research, Professor of Pediatrics, University of Missouri School of Medicine at Kansas City

Updated: Sep 17, 2008

Introduction

Background

Urinary tract infection (UTI) is one of the most common infections of childhood. It distresses the child, concerns the parents, and may cause permanent kidney damage.

In some instances, UTI results in recognition of an important underlying structural or neurogenic abnormality of the urinary tract. The febrile infant or child with clinically significant bacteriuria and no other site of infection to explain the fever, even in the absence of systemic symptoms, has pyelonephritis (ie, upper UTI). Children with a UTI and voiding symptoms, little or no fever, and no systemic symptoms have lower UTI (cystitis).

The site of infection is often unclear when a child with pyuria and clinically significant bacteriuria has another potential source of fever (eg, otitis media, pharyngitis). When UTI is diagnosed in a child, an attempt should be made to identify any risk factors for the UTI (eg, anatomic anomaly, voiding dysfunction, constipation).

Pathophysiology

Almost all UTIs are ascending in origin. Disturbance of the normal periurethral flora, which is part of the host defense against colonization by pathogenic bacteria, predisposes a person to a UTI. Bacteria of the periurethral flora also inhabit the distal urethra. Urine in the proximal urethra, urinary bladder, and other proximal sites in the urinary tract is normally sterile. Uropathogens must gain access to the urinary bladder and proliferate for infection to occur. Uropathogens in the distal urethra may gain access to the bladder because of turbulent urine flow during normal voiding or because of dysfunctional voiding. Successful urinary bladder colonization is unlikely unless bladder defense mechanisms are impaired because normal voiding usually results in an essentially complete washout of contaminating bacteria.

After birth, the periurethral area, including the distal urethra, becomes colonized with aerobic and anaerobic microorganisms that appear to function as a defense barrier against colonization by uropathogens. In early childhood, enterobacteria and enterococci are part of the normal periurethral flora. Escherichia coli is the dominant gram-negative species in young girls, whereas E coli and Proteus species predominate in boys. Children as old as about 5 years are predisposed to have UTIs, partly because of periurethral colonization by E coli, enterococci, and Proteus species. These potential uropathogens usually diminish in the first year of life and are rarely found in children older than 5 years. Studies of girls and women prone to UTI showed that periurethral colonization occurs with the specific bacterium that causes the next infection.

Frequency

International

Studies from Sweden have indicated that at least 3% of girls and 1% of boys have a symptomatic UTI by the age of 11 years. However, data from recent epidemiologic surveys suggest incidences higher than these. Occurrences of a first-time symptomatic UTI are highest for both boys and girls during the first year of life and markedly decrease after that. The minimum cumulative incidence in both boys and girls aged 2 years is slightly over 2%. Most episodes of UTI during the first year of life are pyelonephritis. After 2 years of age first-time UTI manifesting as cystitis is common among girls. More recent data suggest that 8% of girls have a symptomatic UTI during childhood. The incidence of a first UTI in boys older than 2 years is exceedingly low, probably less than 0.5%.

Mortality/Morbidity

Mortality related to UTI is exceedingly rare for otherwise healthy children in developed countries.

Morbidity associated with pyelonephritis is characterized by systemic symptoms, such as fever, abdominal pain, vomiting, and dehydration. Bacteremia and clinical sepsis may occur. Children with pyelonephritis also may have cystitis. Long-term complications of pyelonephritis are hypertension, impaired kidney function, end-stage renal disease (ESRD), and complications of pregnancy (eg, UTI, pregnancy-related hypertension, low-birth-weight neonates).

The voiding symptoms of cystitis are usually transient, clearing within 24-48 hours of effective treatment. Long-term complications of UTI are caused by renal damage secondary to pyelonephritis. Cystitis may cause voiding symptoms and require antibiotics, but it is not associated with long-term deleterious kidney damage.

Race

Data are scant. However, in studies by Hoberman et al, the prevalence of a febrile UTI in Caucasian infants exceeded that of African-American infants.¹ These investigators found that 17% of white female infants younger than 1 year with a temperature of 39°C or more seen in an emergency department had UTIs.

Sex

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, both first-time and recurrent UTIs are most common in girls. The prevalence of UTI in girls between 1 and 2 years of age is 8.1%, in boys it is 1.9%. The rate in circumcised boys is low, 0.2% to 0.4%. The rate in uncircumcised boys is 5 to 20 times higher than in circumcised boys.

In a systematic review, investigators calculated crude estimates of UTI during the first 24 months of life.² Rates were 3% in boys younger than 1 year, 2% in boys older than 1 year, 7% in girls younger than 1 year, and 8% in girls aged 1-2 years.

Age

First-time UTI is most common in the first 2 years of life.

Clinical

History

The 2 broad clinical categories of urinary tract infection (UTI) are pyelonephritis, or upper UTI, and cystitis, or lower UTI. The history and clinical course varies with the patient's age and the specific diagnosis.

• Children aged 0-2 months: Neonates and infants in this age range who have pyelonephritis usually do not have symptoms localized to the urinary tract. UTI is discovered as part of an evaluation for neonatal sepsis.
• Infants and children aged 2 months to 2 years
  • Infants and young children in this age range with pyelonephritis may have a history of unexplained fever (eg, rectal or tympanic membrane–derived temperature of >38°C).
  • These patients are at higher risk for renal injury than are older children, possibly because the lack of localizing signs of infection delays the start of antibiotic therapy. This situation had led to a 3-day rule: An infant or child with unexplained fever should not be observed for more than 3 days without a urine specimen being obtained.
  • Some infants with pyelonephritis in this age range have fever and few other symptoms, whereas others are acutely ill and have a history of irritability, decreased oral intake, abdominal pain, vomiting, and loose bowel movements.
  • Children aged 1-2 years may present with voiding symptoms suggestive of cystitis, with crying on urination or only a foul odor to the urine in the absence of clinically significant fever (temperature <38°C).
• Children aged 2-6 years
  • Children in this age group with febrile UTI (pyelonephritis) usually have systemic symptoms with loss of appetite; irritability; and abdominal, flank, or back pain. Voiding symptoms may be present or absent.
  • Children with acute cystitis have voiding symptoms with little or no temperature elevation. Voiding dysfunction may include urgency, frequency, hesitancy, dysuria, or urinary incontinence.
  • Suprapubic or abdominal pain may be present, and the urine sometimes has a strong or foul odor.
• Children older than 6 years and adolescents
  • UTI among children in this age range usually affects the lower tract, but pyelonephritis also occurs. Symptoms are similar to those in children aged 2-6 years.
  • Girls who have pyelonephritis in infancy or early childhood, including those with persistence of vesicoureteric reflux (VUR), usually have cystitis with UTI when they are older. They are also prone to have a recurrence during pregnancy.

Physical

• Findings on physical examination, such as tenderness in the costovertebral angle or flank, may help localize the site of infection to the kidney. Suprapubic tenderness may be present.
• Infants and younger children with pyelonephritis usually have no localizing findings, but they are febrile and irritable.
• The older children with pyelonephritis often have tenderness of the flank or costovertebral angle, and those with cystitis may have suprapubic tenderness.

Causes

Proliferation of bacteria in the urinary tract is the cause of UTI.

• Infections are almost always ascending in origin and caused by bacteria in the periurethral flora and the distal urethra. These bacteria inhabit the distal GI tract and colonize the perineal area. E coli usually causes a child's first infection, but other gram-negative bacilli and enterococci may also cause infection.
• Staphylococcal infections, especially those due to Staphylococcus saprophyticus, are common causes of UTI among female adolescents.
• Entry of bacteria into the urinary bladder may be the result of turbulent flow during normal voiding, voiding dysfunction, or catheterization. In addition, sexual intercourse or genital manipulation may foster the entry of bacteria into the urinary bladder. More rarely, the urinary tract may be colonized during systemic bacteremia (sepsis); this usually happens in infancy.
• Risk factors for UTI include the following:
  • Children who receive broad-spectrum antibiotics (eg, amoxicillin, cephalexin) that are likely to alter GI and periurethral flora are at increased risk for UTI because these drugs disturb the natural defense against colonization by pathogenic bacteria.
  • Prolonged incubation of bacteria in bladder urine due to incomplete bladder emptying or infrequent voiding compromises an important bladder defense against infection. Symptoms of voiding dysfunction, such as urgency, frequency, hesitancy, dribbling, or incontinence may occur in the absence of infection or local irritation because of uninhibited detrusor contractions. When the child attempts to prevent incontinence during a detrusor contraction by posturing (eg, obstructing the urethra), bacteria-laden urine in the distal urethra may be milked back into the urinary bladder (urethrovesical reflux). This mode of bacterial access is a common risk factor for UTI among pediatric patients who use posturing or pelvic withholding procedures to prevent incontinence.
  • Voiding dysfunction is not usually encountered in a child without neurogenic or anatomic abnormality of the bladder until the child is in the process of achieving daytime urinary control. Children with voiding dysfunction may attempt to prevent incontinence during an uninhibited detrusor contraction by voluntarily increasing outlet resistance. This may be achieved by using various posturing maneuvers, such as tightening of the pelvic-floor muscles, applying direct pressure to the urethra with the hands, or performing the Vincent curtsy, which consists squatting on the floor and pressing the heel of one foot against the urethra.
  • Constipation, with the rectum chronically dilated by feces, is an important cause of voiding dysfunction. Neurogenic or anatomic abnormalities of the urinary bladder may also cause voiding dysfunction.
  • Neonatal circumcision decreases the risk of UTI by about 90% in male infants during the first year of life. The risk of UTI in a circumcised infant is about 1 in 1000 during the first year, whereas an uncircumcised male infant has a 1 in 100 risk of developing a UTI. Given this risk, 111 healthy male infants must be circumcised to prevent 1 UTI. The risk and long-term effect of scarring due to 1 preventable UTI in a male infant are not known.

Differential Diagnoses

Fever in the Toddler
Fever in the Young Infant
Fever Without a Focus
Pyelonephritis
Voiding Dysfunction

Other Problems to Be Considered

Cystitis
Epididymitis
Orchitis
Prostatitis
Urethritis

Workup

Laboratory Studies

• The diagnosis is based onquantitative cultures of a properly collected urine specimen (see Table 1 and Table 2).
  • A midstream, clean-catch specimen may be obtained from children who have urinary control. In the infant or child unable to void on request, the specimen for culture should be obtained by means of suprapubic aspiration or urethral catheterization. Suprapubic aspiration is the method of choice for obtaining urine from the uncircumcised boy with a redundant or tight foreskin and from children of either sex with clinically significant periurethral irritation.
  • A culture of a urinary specimen from a sterile bag attached to the perineal area that shows no or scant growth (<10,000 colony-forming units [CFUs]/mL) is strong evidence of absent urinary tract infection (UTI). However, the false-positive rate is so high that this method of urine collection is not suitable for diagnosing a UTI.
  • Urinalysis does not substitute for urine culture to document the presence of a UTI. However, it can help in identifying febrile children who should receive antibacterial treatment while culture results from a properly collected urine specimen are pending.
• Numerous recent studies have compared dipstick tests for leukocyte esterase and nitrite with microscopic examination of the urinary sediment for bacteria with urinary culture. These studies have been performed to determine whether the dipstick test can eliminate the need for urinary culture. The invasiveness, time involved, and cost of the culture could be eliminated. Current studies report that the specific components of the dipstick test and complete urinalysis cannot detect positive culture findings in all children who have positive urinary culture findings and unexplained fever or voiding symptoms. The conclusion is that urine should be obtained for culture, and initial treatment should be given to those children with fever and a presumptive diagnosis of a UTI, regardless of the result of urinary dipstick testing or urinalysis.^{3,4,5,6,7,8,9}
• Methods of urine collection, examination, and salient findings are shown in Tables 1 and 2. 
  • Table 1. Urinalysis for Presumptive Diagnosis of UTI*

    Method	Findings
    Bright-field or phase-contrast microscopy of centrifuged urinary sediment	Bacteria
    Gram stain of uncentrifuged or centrifuged urinary sediment	Bacteria
    Nitrite and leukocyte esterase test	Positive = UTI likely
    Nitrite test	Positive = UTI probable
    Leukocyte esterase test	Positive = Nonspecific

    *Negative microscopic findings for bacteria do not rule out a UTI, nor do negative results of dipstick testing for nitrite and leukocyte esterase. 
  • Table 2. Quantitative Urine Culture for the Diagnosis of UTI*

    Method	Finding
    Suprapubic aspiration	If a UTI is present, bacteria are likely to be proliferating in bladder urine with growth of any organism except 2000-3000 CFU/mL coagulase-negative staphylococci.
    Catheterization in a girl or midstream clean-void collection in a circumcised boy	Febrile infants and children with UTI usually have >50,000 CFU/mL of a single urinary pathogen; however, UTI may be present with 10,000-50,000 CFU/mL of a single organism.*
    Midstream clean-void collection in a girl or uncircumcised boy	UTI is indicated when >100,000 CFU/mL of a single urinary pathogen is present in a symptomatic patient. Pyuria usually present. A UTI may be present with 10,000-50,000 CFU/mL of a single bacterium.*
    Any method in a girl or boy	If the patient is asymptomatic, bacterial growth is usually >100,000 CFU/mL of the same organism on different days. If pyuria is absent, this result probably indicates colonization rather than infection.

    *Patients with urinary frequency (ie, decreased bladder incubation time) are those most likely to have bacteria proliferating in the urinary bladder in the presence of low colony counts.
• Obtain a CBC count and basic metabolic panel for children with a presumptive diagnosis of pyelonephritis.
• Perform blood cultures in febrile infants and older patients who are clinically ill, toxic, or severely febrile.

Imaging Studies

• General considerations
  • History of imaging: In the past, the recommendation was that an infant or a child with a first febrile UTI should undergo imaging of the urinary tract. In the early years, intravenous pyelography (IVP) and voiding cystourethrography (VCUG) were performed, IVP immediately and VCUG 4-6 weeks later.
  • Ultrasonography: Sonography of the urinary tract subsequently replaced IVP. However, recent studies show that sonograms of the urinary tract obtained after a first febrile UTI seldom provide information that change management. A current recommendation is that urinary sonography should be omitted after a first febrile UTI in infants and children if they respond to treatment (afebrile within 72 h), good follow-up is assured, and no voiding abnormality (no dribbling of urine) or abdominal mass is present. The clinician's judgment should guide the decision regarding imaging studies, as opposed to a rigid rule. Urinary sonography is a safe, noninvasive study that is easy to perform. It is useful in excluding obstructive urography and in identifying children with a solitary or ectopic kidney and some patients with moderate renal damage caused by pyelonephritis.
  • Voiding cystourethrography or nuclear cystography
    • Traditionally VCUG has been recommended for infants and children after a first febrile UTI. This is based on the assumptions that most upper UTIs occur because of urinary bladder infection and that vesicoureteral reflux (VUR) transfers bacteria in the bladder to the kidney. However, using cortical imaging, current data show that upper tract infection occurs equally in children with and without VUR. The assumption that antibacterial prophylaxis prevents a recurrence of UTI seems reasonable, although this has not been proven. A lack of sufficient randomized control studies comparing antibacterial prophylaxis with placebo prohibits an evidence-based recommendation to prevent recurrent UTIs. Long-term, prospective randomized studies are needed.
    • Of note, a first febrile UTI is as frequent in infants with VUR as in those without radiographically demonstrated reflux. The recommendation for VCUG after a first febrile UTI is based on expert opinion and judgment, not on evidence-based guidelines.
    • Some experts suggest that cystography that requires catheterization of the urinary bladder be avoided. Their recommendation, which is not evidence based, is that renal cortical scanning (renal scintigraphy) should be performed. This study helps in identifying kidney injury and/or pyelonephritis. If the scan findings are normal, cystography is not needed. However, if the results are abnormal, VCUG should be obtained.
    • If a VCUG is to be obtained, it should obtained after the voiding pattern returns to its pre-UTI state. If the organism that caused the UTI was susceptible to the antibacterial used to treat the febrile UTI and if the response to therapy was satisfactory, follow-up urinalysis or cultures are not needed. The child should receive antibacterial therapy at least until the cystogram is obtained.
    • Some clinicians recommend waiting 4-6 weeks after febrile UTI is treated to perform VCUG. If the child is given suppressive antibacterial treatment during this period, this recommendation is acceptable. However, recent studies showed that the VCUG may be obtained within the first few days of treating febrile UTI, if the voiding pattern has returned to its pre-UTI state.
  • General recommendation: If imaging studies of the urinary tract are warranted, they should not be obtained until the diagnosis is confirmed with a quantitative urinary culture.
• Summary of imaging recommendations
  • Which children should undergo ultrasonography of the urinary tract after a first febrile UTI?
    • Patients who have a delayed or unsatisfactory response to treatment of the first febrile UTI
    • Children with an abdominal mass or abnormal voiding (dribbling of urine)
    • Any child with a first febrile UTI in whom good follow-up cannot be ensured (Good clinical and experimental data support the opinion that the best way to prevent kidney damage due to a UTI is by prompt diagnosis and effective treatment of a febrile UTI.)
    • Children with a first febrile UTI caused by an organism other than E coli
    • Children with recurrence of a febrile UTI after they have a satisfactory response to treatment of the initial febrile UTI
  • Which children should undergo VCUG after a first febrile UTI?
    • Those in whom treatment fails after 48-72 hours
    • Patients with an abnormal voiding pattern (dribbling of urine)
    • Infants and children in whom good follow-up is not assured
    • Those with an abdominal mass
    • Infants and children with recurrence of a febrile UTI
  • Which pediatric patients do not need imaging studies after a first UTI?
    • Infants and children with a first febrile UTI who are assured follow-up, who respond promptly to treatment (afebrile within 72 h), and who have a normal voiding pattern (no dribbling) and no abdominal mass
    • Infants and children with cystitis: Those with an abnormal voiding pattern after receiving effective treatment of the UTI may need to undergo an evaluation for voiding dysfunction; this may include standard VCUG.

Treatment

Medical Care

• Infants younger than 8 weeks with a febrile urinary tract infection (UTI)
  • The diagnosis is usually based on fever and positive results form a urine specimen obtained by catheterization. Infants with such findings are usually hospitalized and receive parenteral antibiotic therapy (see Table 3 below). However, clinical judgment may indicate that home treatment is appropriate. Parenteral antibiotics may be used with daily follow-up until the patient is afebrile for 24 hours. Complete 10-14 days of therapy with an oral antibiotic active against the infecting bacteria. 
  • Table 3. Antibiotic Agents for Parenteral Treatment of a UTI

    Drug	Dosage and Route	Comment
    Ceftriaxone	50-75 mg/kg/d IV/IM as a single dose or divided q12h	Do not use in infants <6 wk of age; parenteral antibiotic with long half-life; may displace bilirubin from albumin
    Cefotaxime	150 mg/kg/d IV/IM divided q6-8h	Safe to use in infants <6 wk of age; used with ampicillin in infants aged 2-8 wk
    Ampicillin	100 mg/kg/d IV/IM divided q8h	Used with gentamicin in neonates <2 wk of age; for enterococci and patients allergic to cephalosporins
    Gentamicin	Term neonates <7 d: 3.5-5 mg/kg/dose IV q24h Infants and children <5 y: 2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h Children >5 y: 2-2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h	Monitor blood levels and kidney function if therapy extends >48 h

    Note.—IM = intramuscular; IV = intravenous; q = every.
• Infants and children aged 2 months to 2 years with a first febrile UTI
  • If clinical findings indicate that immediate antibiotic therapy is indicated, a urine specimen for urinalysis and culture should be obtained by means of suprapubic aspiration or catheterization before treatment is started.
  • Recent evidence suggests no significant differences in efficacy between IV antibiotic therapy given for 3 days followed by oral therapy for another 11 days and 14 days of oral therapy. These data are based on a randomized control trial of 306 children aged 1-24 months to compare oral cefixime for 14 days with IV cefotaxime for 3 days followed by oral cefixime for 11 days. No notable differences were observed in short- or long-term outcomes (eg, clinical response, reinfection, renal scars at 6 mo). These data led to the recommendation that children with a febrile UTI should receive oral treatment with a second- or third-generation cephalosporin, amoxicillin clavulanate, or sulfamethoxazole-trimethoprim (SMZ-TMP) (see Table 4). 
  • Table 4. Antibiotic Agents for the Oral Treatment of UTI

    Antibacterial Agent	Daily Dosage
    Sulfisoxazole	120-150 mg/kg divided q4-6h
    Sulfamethoxazole and trimethoprim	6-12 mg/kg TMP, 30-60 mg/kg SMZ divided q12h
    Amoxicillin and clavulanic acid	20-40 mg/kg divided q8h
    Cephalexin	20-50 mg/kg divided q6h
    Cefixime	8 mg/kg divided q12-24h
    Cefpodoxime	10 mg/kg divided q12h
    Loracarbef	15-30 mg/kg divided q12h
    Nitrofurantoin*	5-7 mg/kg divided q6h

    *Nitrofurantoin may be used to treat lower UTIs. However, because of its limited tissue penetration, nitrofurantoin is not suitable for the treatment of kidney infection.
  • A child treated with oral antibiotics should not be acutely ill or toxic, and he or she should not have persistent vomiting or moderate-to-severe dehydration.
• Daily follow-up and good compliance is essential with this management.
• Inpatient treatment of children with complicated pyelonephritis
  • Provide appropriate parenteral fluids, usually at 1-1.5 times the usual maintenance rate.
  • Parenteral treatment with a third-generation cephalosporin, such as ceftriaxone or cefotaxime (Table 3). Add ampicillin if gram-positive cocci are present in the urinary sediment or if no organisms are observed. Gentamicin is an alternative for term infants older than 7 days, for older children, and for adolescents who are allergic to cephalosporins. Monitor renal function and blood aminoglycoside levels if this medication is required for more than 48 hours.
  • Results of urine culture and sensitivity studies are usually available within 48 hours. If the pathogen is sensitive to the antibiotic used and if the child is improving, continue treatment with the parenteral route until the child is afebrile for 24-36 hours. An oral antibiotic that is effective against the infecting organism may then be substituted for parenteral therapy (see Table 4).
  • The hospitalized patient is usually ready to go home after 48-72 hours. Continue therapeutic doses of antibiotics for a total of 10-14 days of antibiotic therapy. Antibacterial therapy should be given to prevent reinfection (see Table 5 below) and continue at least until a VCUG is obtained (if one is to be obtained). 
  • Table 5. Antibiotic Agents to Prevent Reinfection

    Agent	Single Daily Dose
    Nitrofurantoin*	1-2 mg/kg PO
    Sulfamethoxazole and trimethoprim*	1-2 mg/kg TMP, 5-10 mg/kg SMZ PO
    Trimethoprim	1-2 mg/kg PO

    *Do not use nitrofurantoin or sulfa drugs in infants younger than 6 weeks. Reduced doses of an oral first-generation cephalosporin, such as cephalexin at 10 mg/kg, may be used until the child reaches the age of 6 weeks. Ampicillin or amoxicillin are not recommended because of the high incidence of resistant E coli.
• Children with cystitis
  • Children with cystitis usually do not require special medical care other than appropriate antibiotic therapy and symptomatic therapy if the voiding symptoms are marked. Antibiotic therapy is started on the basis of the practitioner's appraisal of the patient's clinical history and urinalysis results before the diagnosis is documented. Systematic reviews of treatments for cystitis in children showed no difference in the efficacy with 7-14 days of therapy compared with 2-4 days. Single-dose or single-day therapy is not recommended in children with cystitis.
  • Symptomatic relief for dysuria consists of increasing fluid intake to enhance urine dilution and output, acetaminophen, and nonsteroidal anti-inflammatory drugs. If voiding symptoms are severe and persistent, add phenazopyridine hydrochloride (Pyridium). Do not administer phenazopyridine hydrochloride for longer than 48 hours because of the risk of methemoglobinemia, hemolytic anemia, and other adverse reactions.
  • Sitting in a tub of warm water for 20-30 minutes 3-4 times a day often affords symptomatic relief. Patients with severe voiding discomfort may obtain relief by using an appropriately sized rectal suppository of belladonna and opium. Inform the patient to use these suppositories no more than 4 times a day and for no longer than 2 days.
  • A 4-day course of an oral antibiotic agent is recommended for the treatment of cystitis (see Table 4). If the clinical response is not satisfactory after 2-3 days, alter therapy on the basis of antibiotic susceptibility.

Medication

Antibiotics are used to treat urinary tract infection (UTI) and to prevent recurrences. Avoid nephrotoxic drugs whenever possible. On occasion, analgesic therapy may be used to provide relief because of voiding symptoms.

Antibiotic agents

These are used for bacterial infections of the urinary tract. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Ceftriaxone (Rocephin)

Initial parenteral therapy for complicated pyelonephritis in pediatric patients beyond neonatal period.

Dosing

Adult

1-2 g IV/IM q12-24h

Pediatric

Infants and children: 50-75 mg/kg/d IV/IM divided q12-24h

Interactions

Decreased elimination half-life with coadministration of high-dose probenecid; possible increased risk of nephrotoxicity with aminoglycosides

Contraindications

Documented hypersensitivity; jaundice; neonates, particularly hyperbilirubinemic premature infants

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to penicillin, gallbladder, biliary tract, liver, or pancreatic disease, colitis; avoid in neonates (especially if premature) due to potential for bilirubin displacement

Cefotaxime (Claforan)

Used as initial parenteral therapy for pediatric patients with acute complicated pyelonephritis. May be used for neonates or jaundiced patients. In infants, 2- to 8-wk regimen also includes ampicillin. Requires dosing q6-8h.

Dosing

Adult

1-2 g IV/IM q6-8h

Pediatric

0-4 weeks and <1200 g: 100 mg/kg/d IV/IM divided q12h
>7 days and 1200-2000 g: 150 mg/kg/d IV/IM divided q8h
>7 days and >2000 g: 150 mg/kg/d IV/IM divided q6-8h

Interactions

Increased concentrations with coadministration of probenecid

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to penicillin, impaired renal function, history of colitis

Ampicillin (Marcillin, Omnipen, Polycillin)

Parenteral therapy for initial treatment of patients with acute pyelonephritis, with gram-positive cocci in urinary sediment, or when no organisms observed.

Dosing

Adult

500 mg IV/IM q4-6h

Pediatric

100-200 mg/kg/d IV/IM divided q4-6h

Interactions

Increased concentrations with coadministration of probenecid

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to cephalosporin; dosage modification needed with impaired kidney function

Amoxicillin and clavulanate (Augmentin)

PO therapy for completion of initial treatment of infection with susceptible organism. Amoxicillin inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase producing bacteria.
Good alternative antibiotic for patients allergic or intolerant to macrolide class. Usually well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma or and Legionella species. Half-life of PO dosage form 1-1.3 h. Has good tissue penetration but does not enter CSF.
For patients >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin–clavulanic acid ratios in 250-mg tab (250-125) vs 250 mg chewable-tab (250-62.5), do not use 250-mg tab until child weighs >40 kg.

Dosing

Adult

500-875 mg q12h PO or 250-500 mg PO q8h for 7-10 d

Pediatric

<3 months: 125 mg/5 mL PO susp; 30 mg/kg/d (based on amoxicillin component) divided bid for 7-10 d
>3 months: if 200 mg/5 mL or 400 mg/5 mL susp used, 45 mg/kg/d PO divided q12h; 125 mg/5 mL or 250 mg/5 mL susp used, 40 mg/kg/d PO divided bid for 7-10 d
>40 kg: Administer as in adults

Interactions

Coadministration with warfarin or heparin increases risk of bleeding; may act synergistically against selected microorganisms when coadministered with aminoglycosides; coadministration with allopurinol may increase incidence of amoxicillin rash; may decrease efficacy of PO contraceptives when administered concomitantly

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Diarrhea may occur; adjust dose in renal impairment; cross-allergy may occur with other beta-lactams and cephalosporins

Gentamicin (Garamycin)

Initial parenteral therapy for patients with bacterial pyelonephritis who are allergic to cephalosporins. For complicated UTI, sometimes used in combination with a cephalosporin.

Dosing

Adult

3-6 mg/kg/d IV/IM divided q8h

Pediatric

Premature neonate and <1000 g: 3.5 mg/kg/dose IV/IM q48h
Term neonate and <7 days: 3.5-5 mg/kg/dose IV q24h
Infants and children <5 years: 2.5 mg/kg/dose IV q8h
Children >5 years: 2-2.5 mg/kg/dose IV q8h

Interactions

Increased toxicity with concurrent use of amphotericin B, cephalosporins, penicillins, loop diuretics, vancomycin, cisplatin, indomethacin; potentiates neuromuscular blocking agents and botulinum toxin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in neonates; caution in renal impairment, auditory or vestibular impairment, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; dosage modification needed with renal impairment

Sulfisoxazole (Gantrisin)

PO treatment for bacterial UTI. Sulfonamide derivative that exerts bacteriostatic action by antagonizing para-aminobenzoic acid (PABA), an essential component in folic acid synthesis.

Dosing

Adult

2-4 g PO initially, then 4-8 g/d PO divided q4-6h

Pediatric

<2 months: Contraindicated
>2 months: 75 mg/kg PO loading dose, then 120-150 mg/kg/d PO divided q4-6h; not to exceed 6 g/d

Interactions

May enhance anticoagulation action effects of warfarin and cause hemorrhage; may enhance anesthetic effects of thiopental; risk of nephrotoxicity may increase with concurrent cyclosporine; may increase serum hydantoin levels when administered concurrently; may enhance methotrexate-induced bone marrow when administered concurrently; may increase sulfonylurea concentrations and cause hypoglycemia in diabetes; may prolong bioavailability of tolbutamide when administered concurrently; coadministration with diuretics may increase incidence of thrombocytopenia with purpura
Concurrent administration with indomethacin may increase free drug concentration of sulfonamide; sulfonamides may form precipitate in acidic urine when used concomitantly with methenamine mandelate; probenecid and salicylates may displace sulfonamides from plasma albumin, increasing free-drug concentrations and potentiating its toxicity

Contraindications

Documented hypersensitivity; porphyria; urinary tract obstruction; infants <2 mo; pregnant women in third trimester; nursing mothers

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pregnancy category D near term because of potential displacement of bilirubin causing kernicterus; G-6-PD deficiency; hepatic or renal impairment; dosage modification and concern about crystalluria with impaired renal function

Sulfamethoxazole and trimethoprim (Bactrim, Cotrim, Septra)

PO treatment for bacterial UTI and for prevention of reinfection.

Dosing

Adult

UTI: TMP 160 mg–SMZ 800 mg (ie, 1 double-strength tab) PO q12h for 10-14 d

Pediatric

<2 months: Contraindicated
>2 months:
UTI: 6-12 mg/kg/d (based on trimethoprim component) PO divided q12h
Reinfection prophylaxis: 1-2 mg/kg/d (based on trimethoprim component) PO qd

Interactions

Decreases clearance of warfarin; displacement of methotrexate from protein binding sites; increases effect of sulfonylureas, phenytoin, and thiopental; decreases serum cyclosporine concentrations

Contraindications

Documented hypersensitivity; porphyria; megaloblastic anemia due to folate deficiency; age <2 mo

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Pregnancy category D near term because of potential displacement of bilirubin causing kernicterus; G-6-PD deficiency; impaired renal or hepatic function; dosage adjustment needed with renal impairment

Cephalexin (Biocef, Cefanex, Keflex)

PO treatment for bacterial UTI and for prevention of infection in infants <6-8 wk.

Dosing

Adult

250-500 mg PO q6h

Pediatric

<6-8 weeks: 20-50 mg/kg/d PO divided q6h
Prophylaxis: 10 mg/kg/d PO qd

Interactions

Probenecid increases serum concentrations; coadministration with aminoglycosides increases nephrotoxic potential

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity with penicillin; colitis; dosage modification needed with renal impairment

Cefixime (Suprax)

PO treatment for acute bacterial UTI. By binding to 1 or more penicillin-binding proteins, arrests bacterial cell-wall synthesis and inhibits bacterial growth.

Dosing

Adult

400 mg/d PO divided q12-24h

Pediatric

8 mg/kg/d PO q12-24h; not to exceed 400 mg/d

Interactions

Probenecid increases serum concentration; coadministration of aminoglycosides increases nephrotoxicity; may increase serum carbamazepine concentration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to penicillin; impaired renal function; colitis; dosage modification needed with impaired renal function

Cefpodoxime (Vantin)

PO treatment for acute bacterial UTI. Indicated to manage infections caused by susceptible mixed aerobic-anaerobic microorganisms.

Dosing

Adult

100-400 mg/dose PO q12h

Pediatric

>6 months to 12 years: 10 mg/kg/d PO divided q12h
>12 years: Administer as in adults

Interactions

Reduced absorption with coadministration of antacids and H2-receptor antagonists; reduced renal excretion with probenecid

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to penicillin; colitis; impaired renal function; with impaired renal function, reduce dosage by one half if CrCl 10-30 mL/min and by three fourths if <10 mL/min (high doses may cause CNS toxicity); bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Loracarbef (Lorabid)

PO treatment for acute bacterial UTI. Beta-lactam antibiotic, which inhibits bacterial cell-wall synthesis by binding to 1 or more penicillin-binding proteins. Inhibits final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, inhibiting cell-wall biosynthesis.

Dosing

Adult

Acute pyelonephritis: 400 mg PO q12h for 14 d
Lower UTI: 200 mg PO qd for 7 d

Pediatric

6 months to 12 years: 15-30 mg/kg/d PO divided q12h
>12 years: Administer as in adults

Interactions

Inhibited renal excretion with probenecid; aminoglycosides may have additive nephrotoxic effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to other beta-lactam antibiotics (eg, penicillins, cephalosporins); colitis; dosage modification needed with impaired renal function

Nitrofurantoin (Furadantin, Macrobid, Macrodantin)

PO treatment of bacterial lower UTI (cystitis) and for prevention of reinfection. Synthetic nitrofuran; interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

Dosing

Adult

Acute UTI: 50-100 mg PO q6h
Prevention of reinfection: 50-100 mg PO qhs

Pediatric

Lower UTI: 5-7 mg/kg/d PO divided q6h
Prevention of reinfection: 1-2 mg/kg/d PO divided q12-24h

Interactions

Decreases renal secretion with probenecid; decreases rate and extent of absorption with antacids; drugs that delay gastric emptying (eg, anticholinergics) increase absorption

Contraindications

Documented hypersensitivity; renal impairment; age <1 mo

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

G-6-PD deficiency; may cause severe and irreversible peripheral neuropathy that can be fatal; renal impairment, diabetes, electrolyte imbalance, anemia, and vitamin B deficiency increase risk for adverse effects; prolonged use of antibiotics may result in fungal or bacterial overgrowth of resistant or nonsusceptible organisms

Trimethoprim (Proloprim, Trimpex)

PO antibiotic to prevent UTI. Dihydrofolate reductase inhibitor that prevents production of tetrahydrofolic acid in bacteria. Active in vitro against broad range of gram-positive and gram-negative bacteria, including uropathogens, eg, Enterobacteriaceae and Staphylococcus saprophyticus. Resistance usually mediated by decreased cell permeability or alterations amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production.

Dosing

Adult

Prophylaxis: 100 mg PO qd

Pediatric

Prophylaxis: 1-2 mg/kg PO qd

Interactions

Increased risk of folate deficiency with coadministration of other folate antagonists (eg, methotrexate, pyrimethamine); increased serum levels of phenytoin, cyclosporine, dapsone, procainamide, rifampin, and warfarin

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Impaired renal or hepatic function or possible folate deficiency; decreased dose needed with renal dysfunction

Systemic analgesics

These agents are used to provide relief from voiding symptoms due to UTI.

Acetaminophen (Tylenol, Panadol, Tempra)

Nonopioid systemic analgesic used for moderate voiding discomfort caused by UTI.

Dosing

Adult

325-650 mg PO q4-6h

Pediatric

Neonates: 10-15 mg/kg PO q6-8h
Infants and children: 10-15 mg/kg PO q4-6h

Interactions

Hepatic toxicity increased by enzyme inducers (eg, barbiturates, carbamazepine, phenytoin, alcohol; especially long-term use); coadministration of rifampin may decrease therapeutic effect

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Avoid products containing aspartame with phenylketonuria; many nonprescription products contain acetaminophen, query patient about their use; concentrations of products vary, prescribe precise dose in milligrams

Urinary bladder analgesics

These agents are used to relieve burning, spasticity, and pain during voiding due to UTI.

Phenazopyridine (Azo-Standard, Pyridium, Urodine)

Exerts local topical anesthetic or analgesic action on urinary mucosa. Used for symptomatic relief of pain, burning, urgency, frequency, and other discomforts arising from irritation of lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, passage of sound, or catheters. Analgesic action may reduce or eliminate need for systemic analgesics.

Dosing

Adult

100-200 mg PO q4-6h for 2 d

Pediatric

12 mg/kg/d PO divided q8h for 2 d

Interactions

May cause false-negative results for Clinistix, Tes-tape, Ictotest, Acetest, Ketostix, or urinalysis tests based on spectrometry or color reactions

Contraindications

Documented hypersensitivity; liver or kidney disease; do not use if CrCl <50 mL/min

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Impaired renal function; administer after meals; will likely discolor urine

Follow-up

Further Inpatient Care

• For patients with pyelonephritis, give a suppressive dose of antibiotics to prevent reinfection at least until the VCUG is obtained (if one is to be obtained) (see Table 5).
• In patients with pyelonephritis, some clinicians discontinue antibacterial therapy 1-2 days after VCUG, if no VUR is present.
  • However, in studies of cortical scanning, roughly one half of the children with an initial episode of pyelonephritis have VUR, and one half have no radiographically identifiable reflux. Reinfection is common in both groups, with a high incidence in the first 6 months after the initial infection.
  • Until evidence-based guidelines about the use of suppressive antibacterial therapy after an initial febrile urinary tract infection (UTI) are available, recommending 6-12 months of suppressive treatment seems reasonable. Patients with VUR of grade III should receive a prolonged course of suppressive therapy. Patients VUR of grade IV or worse should be referred to a pediatric nephrologist or urologist.

Further Outpatient Care

• For children with uncomplicated acute pyelonephritis
  • Although children with a febrile UTI may qualify for outpatient care, they still are at risk for kidney damage. Initial use of a parenteral antibiotic may increase the likelihood of promptly ceasing the bacterial proliferation in the renal tissue. However, Hoberman et al (1999) indicated that oral therapy with a third-generation cephalosporin was as effective as traditional inpatient treatment with parenteral antibacterial therapy.
  • If the patient is not allergic to a cephalosporin, initial treatment may consist of a single dose of ceftriaxone 75 mg/kg IV/IM q12-24h.
  • If the patient is allergic to cephalosporin, initial treatment may be gentamicin 2.5 mg/kg IV/IM as a single dose.
  • Start treatment with an oral antibacterial agent at therapeutic doses within the next 12-18 hours if the patient's response is satisfactory.
  • Arrange for follow-up, usually telephone follow-up, at 24 hours to monitor the response to treatment and at 48 hours to modify treatment the results of antibacterial sensitivity studies indicate a need to change.
  • Arrange for a follow-up visit after 7-10 days to check the patient's clinical course.

Deterrence/Prevention

• Avoid unnecessary use of antibiotics for upper respiratory infections and otitis media. Antibiotics can alter GI and periurethral flora and compromise natural defenses against colonization by pathogenic agents.
• Treat voiding dysfunction, especially when it is associated with posturing, which can lead to urethrovesical reflux and recurrence of UTIs.
• Consider circumcision of male neonates.

Complications

• An allergic reaction to antibiotic therapy is a risk.
• Children with pyelonephritis may develop lobar inflammation of the kidney (lobar or focal nephronia) or renal abscess.
• Any inflammation of the renal parenchyma may lead to scar formation.
• Long-term complications of pyelonephritis are hypertension, impaired renal function, ESRD, and complications of pregnancy (eg, UTI, pregnancy-related hypertension, low-birth weight neonates).

Prognosis

• In industrialized countries, kidney damage with long-term complications as a consequence of UTI per se is currently less common than in the early 20th century, when pyelonephritis was a frequent cause of hypertension and ESRD in young women.
  • This change is probably a result of improved overall healthcare and close follow-up of children after an episode of pyelonephritis.
  • In countries with high-quality healthcare, hypertension, impaired renal function, and ESRD are now most commonly encountered in infants with intrauterine renal damage.
• Clinically significant urinary tract abnormalities are frequently identified using intrauterine ultrasonography. After birth, these children may incur additional kidney damage as a result of postnatal infection, but UTI is not the major cause of the kidney impairment. The major causes of impaired kidney function are developmental abnormalities.

Patient Education

• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Urinary Tract Infections and Bladder Control Problems.

Miscellaneous

Medicolegal Pitfalls

• Medical legal confrontations related to the management of children with urinary tract infection (UTI) appear to be uncommon, but they definitely occur.
• Administration of an antibiotic to a child known to be allergic to that medication can result in a severe reaction and is a potential cause of medical legal action.

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Keywords

urinary tract infection, UTI, cystitis, pyelonephritis, urethritis, urinary tract abnormality, bacteriuria, upper urinary tract infection, lower tract urinary infection, pyuria, uropathogens, periurethral colonization, Escherichia coli, E coli, Proteus, enterococci, impaired kidney function, end-stage renal disease, ESRD, urgency, frequency, hesitancy, dysuria, urinary incontinence, suprapubic pain, abdominal pain, foul odor to urine, vesicoureteric reflux, VUR, Staphylococcus saprophyticus, catheterization, voiding dysfunction, incomplete bladder emptying, infrequent voiding, incontinence, dribbling

Contributor Information and Disclosures

Author

Stanley Hellerstein, MD, Pediatric Nephrologist, Children's Mercy Hospital of Kansas City; Ernest L Glasscock, MD Chair in Pediatric Research, Professor of Pediatrics, University of Missouri School of Medicine at Kansas City
Stanley Hellerstein, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, and American Society of Pediatric Nephrology
Disclosure: Nothing to disclose.

Medical Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

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