AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Urinary tract infections (UTIs) are relatively common infections in children. Cystitis (lower-tract infection) is characterized by voiding-related symptoms with or without fever and often without other systemic signs. Findings on nuclear renal scans suggest that the vast majority of infants and young children with febrile UTIs have acute pyelonephritis (APN), which is an upper-tract infection.

Early recognition and prompt treatment of UTIs is important to prevent late sequelae, such as renal scarring, hypertension, and renal failure. When assessing the pediatric patient with UTI, one may encounter few specific symptoms. Older children are most likely to have symptoms attributable to the urinary tract. Differentiating cystitis from pyelonephritis in the pediatric patient may be difficult and sometimes impossible. Febrile UTI should be assumed to be pyelonephritis and treated accordingly.

Pathophysiology

UTIs are generally ascending in origin and caused by perineal contaminants, usually bowel flora. However, in neonates, infection is assumed to be hematogenous in origin rather than ascending. This feature may explain the nonspecific symptoms associated with UTI in these patients. After the neonatal period, bacteremia is generally not the source of infection; rather, UTI or pyelonephritis is the cause of the bacteremia.

Bacterial colonization of the bladder is most likely to develop into infection if urinary stasis or low-flow conditions are present. Some causes of these conditions include infrequent voiding, incomplete voiding, vesicoureteral reflux (VUR), obstruction or other urinary tract abnormalities. Even in the absence of urinary tract abnormalities, cystitis may result in VUR or worsen preexisting VUR and lead to pyelonephritis. Chronic or recurrent pyelonephritis results in renal damage, scarring, and, if severe, chronic renal failure.

Frequency

United States

The prevalence varies by age and sex. About 60-65% of children with febrile UTIs have APN. In general, 2.7-4.1% of children younger than 2 years who have fever also have UTI, even if another source is identified. In Caucasian girls younger than 2 years with fever (temperature >39°C), 17% have UTI.

Mortality/Morbidity

Acute mortality is uncommon and is related to sepsis.

• Generalized bacteremia or sepsis may develop from pyelonephritis. In patients younger than 2 years with APN, 8-10% have bacteremia.
• Acute renal parenchymal injury occurs in 20-90% of children with APN. About 40% of these children have long-term renal scarring, which may lead to hypertension and renal insufficiency. Treatment of pyelonephritis within the first 5-7 days after onset is necessary to prevent renal damage.
• Impaired renal tubular function and secondary pseudohypoaldosteronism may develop in infants with pyelonephritis. Infants may develop hyperkalemia and hyponatremia.

Race

The prevalence of urinary infection is 5-fold greater in white children than in African American children and 2-fold greater than in children of other races.

Sex

• The prevalence of UTI in uncircumcised boys is eight times greater than that of circumcised boys in the first year of life. In addition, the incidence of UTI is higher in uncircumcised male infants than in female infants.
• After age 12 months, UTIs are more frequent in girls than in boys.

Age

• In neonates, infection is generally hematogenous in origin.
• Girls younger than 11 years have a 3-5% risk of infection. For boys younger than 11 years, the risk is 1%.
• Febrile infants are as likely to have UTI as a source of fever as they are to be bacteremic. Both are observed in about 6-8% of patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Signs and symptoms of UTI and pyelonephritis vary with the age of the patient.
• Neonates often present with nonspecific symptoms of jaundice, hypothermia or fever, poor feeding, vomiting, and failure to thrive. Neonates, especially male newborns, may develop hyponatremia and hyperkalemia as a result of secondary pseudohypoaldosteronism.
• Infants and young children aged 2 months to 2 years often present with nonspecific symptoms of fever lasting longer than 48 hours, poor feeding, vomiting, and diarrhea. Their urine may be malodorous; hematuria may be noted.
• Preschoolers and school age children present with fever for greater than 48 hours. They may complain of abdominal pain or flank pain. Vomiting, diarrhea, and anorexia may be present. Their urine is typically malodorous, and hematuria may be noted. Voiding-related symptoms including enuresis, dysuria, urgency, and frequency, may occur but need not be present.
• Adolescents are most likely to present with classic adult symptoms of fever, often with chills, rigors, and flank pain. They may have abdominal and suprapubic pain, along with voiding-related symptoms of frequency, dysuria, and hesitancy. Their urine is most often malodorous, though hematuria is variably present.

Physical

Because many symptoms of pyelonephritis are nonspecific, complete physical examination is necessary to exclude other causes of the patient's symptoms. Specific findings are as follows:

• General appearance
• • Most infants and children are uncomfortable and appear ill.
  • Older children and adolescents may be mildly to moderately ill.
• Vital signs
• • Fever may be present, with body temperature of more than 38°C and often more than 39°C.
  • Tachycardia may be present, secondary to fever and pain.
  • Blood pressure is usually normal. Hypertension should raise concern for clinically significant obstruction or renal parenchymal disease. Hypotension may occur if sepsis and shock are present.
• Abdominal findings
• • Abdominal pain may be present.
  • A mass may indicate obstruction, hydronephrosis, or another anatomic abnormality.
  • Suprapubic pain may be present, though this is more common with cystitis than with polynephritis.
  • A palpable bladder indicates obstruction or functional difficulty in starting or completing voiding.
  • Adolescent girls may have right upper quadrant pain similar to that observed in patients with cholecystitis.
• Back findings
• • Tenderness in the costovertebral angle (CVA), back, or flank is likely to be present in older children and adolescents.
  • Sacral dimple or birthmarks overlying the spine may be associated with an underlying anomaly of the spinal cord.
  • Vertebral abnormalities may be evident.
• Genitourinary findings
• • Assess for irritation, pinworms, vaginitis, trauma, or signs of sexual abuse.
  • A bulging hymen suggests an imperforate hymen and urethral obstruction.
• Neurologic findings: Weak lower extremities or diminished reflexes may be signs of spinal-cord dysfunction, and they may be associated with a neurogenic bladder.

Causes

• Bacterial pathogens are the most common cause of pyelonephritis.
• • Escherichia coli - By far the most common organism, causing more than 90% of all cases of APN.
  • Klebsiella oxytoca and species
  • Proteus species
  • Enterococcus faecalis and species
  • Gram-positive organisms, including staphylococcal species and group B Streptococcus - Rare causes of APN
• Bacteremia is the leading cause of infection in neonates, whereas ascending infection from bacteriuria involving the lower urinary tract predominates in other age groups.
• VUR increases the risk for pyelonephritis.
• Delayed or incomplete voiding, as seen with neurogenic bladder or obstruction, increases the risk for urinary stasis and overgrowth of colonizing bacteria.
• Catheterization may increase the risk of introducing periurethral bacteria into the bladder. Clean intermittent catheterization leads to colonization of the bladder that might lead to pyelonephritis if stasis allows any infection to ascend.
• Constipation may impair bladder emptying leading to stasis and ascending infection.
• Boys who are uncircumcised have a risk of UTI 2.2% higher than that of uncircumcised boys. The risk of APN is not established.
• Sexual activity may cause urethral inflammation, lead to bladder colonization, and increase the risk for APN.
• VUR increases the risk for and size of renal cortical lesions, though clinically significant lesions can develop in the absence of VUR.
• Familial inheritance of susceptibility to pyelonephritis may be related to chemokine receptor inheritance.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Concurrent pregnancy
Anatomic abnormalities of the urinary tract
VUR
Ureteropelvic junction obstruction
Posterior urethral valves
Ureterocele
Vaginitis
Fever of unknown origin
Pelvic inflammatory disease
Xanthogranulamatous pyelonephritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urinalysis
• • Urine must be collected with proper technique to be useful for diagnosing cystitis or APN. Suprapubic bladder aspiration should be performed in uncircumcised male patients in whom the urethral meatus is not visible, as well as in infants with periurethral irritation. Bladder catheterization is the appropriate technique for obtaining a urine sample in most infants and young children. A clean-catch, midstream urine sample may be obtained in children who can cooperate and void on request. A specimen collected by using sterile bag may be used for urinalysis but not urine culture.
  • A urine specimen that is positive for nitrite, leukocyte esterase, or blood may indicate UTI.
  • Microscopic examination of an unspun sample that contains more than 10 WBCs per high-powered field or any bacteria is highly predictive of a positive urine culture. RBC or WBC casts suggest underlying renal parenchymal disease. Epithelial cells suggest skin contamination.
  • A normal result from urinalysis does not exclude pyelonephritis.
• Urine culture
• • Urine cultures must be obtained in all children with suspected pyelonephritis. Treatment should not be commenced on the basis of urinalysis results, and normal urinalysis findings do no exclude an infection. APN may be present even if urine cultures demonstrate no growth.
  • A clean-catch urine specimen with more than 100,000 colony-forming units (CFUs) of a single organism is considered diagnostic of a UTI. Organisms, such as Lactobacillus, Staphylococcus, or Corynebacterium species may not be clinically relevant.
  • Cultures showing more than 100,000 CFUs of a single organism obtained by means of transurethral catheterization demonstrate is 95% sensitive and 99% specific for UTI. Specimens growing 10⁴ CFUs may be consistent with infection, but the test should be repeated if infection is not likely and if treatment has not yet commenced.
  • Cultures from bagged urine specimens are useful only if no growth is observed. Bagged urine specimens result in a false-positive rate of 85%. Before treatment is started on the basis of results from a bagged-specimen test, a catheterized or suprapubic specimen should be obtained.
  • Structural abnormalities of the urinary tract may be associated with infections secondary to multiple organisms or unusual gram-negative bacteria, such as Pseudomonas aeruginosa.
• Electrolyte measurements
• • Some patients may have abnormalities, which may be secondary to vomiting or diarrhea. In cases of recurrent or chronic infection, renal scarring may lead to renal failure.
  • Secondary pseudohypoaldosteronism may develop, with impaired renal tubular function, in infants with pyelonephritis. Mild hyponatremia and hyperkalemia may be present. Infants with underlying urinary-tract anomalies have an increased risk of this electrolyte imbalance, which resolves when the infection is treated.
• Renal function testing: An increased BUN and/or creatinine level should raise the suspicion for hydronephrosis or renal parenchymal disease.
• Determination of inflammatory markers
• • An elevated WBC count is nonspecific and does not help in distinguishing lower UTI from upper UTI.
  • In the presence of a febrile UTI, a erythrocyte sedimentation rate (ESR) of more than 30 mm/h is highly predictive of APN.
  • C-reactive protein (CRP) levels are correlated with parenchymal defects on dimercaptosuccinic acid (DMSA) scanning. Elevated CRP concentrations are sensitive but nonspecific markers of renal parenchymal involvement in the febrile infant and child with UTI. CRP values may be used to distinguish bladder colonization from APN in a febrile child with bacteriuria and a neurogenic bladder.
  • Serum procalcitonin
  • • Procalcitonin is an acute inflammatory marker with a sensitivity of 70-95% and a specificity that approaches 90% for renal involvement compared with results of DMSA scan in infants and children with febrile UTI. Although less sensitive than CRP, procalcitonin is more specific for the diagnosis of APN. Procalcitonin values are better correlated with long-term renal scarring than CRP.
    • Procalcitonin levels near 0.5 ng/mL may not consistently correlate with APN. As procalcitonin levels increase, the severity of renal lesions on DMSA increases.
    • Higher levels of procalcitonin predict VUR in infants and children at the onset of pyelonephritis.
  • Serum and urinary interleukin-6 and interleukin-8 are correlated with renal involvement in infants and children with UTI with high sensitivity (81-88%) and acceptable specificity (78-83%). These markers are not reliable in neonates with suspected APN.

Imaging Studies

• Radiography
• • Radiographic studies are generally not indicated to diagnose APN.
  • Studies may be indicated if the child's condition does not respond to treatment as expected and if colonization must be distinguished from infection in the patient with chronic bacteriuria.
  • Guidelines from the American Academy of Pediatrics recommend imaging after first febrile UTIs in infants and young children to identify abnormalities that may predispose them to recurrent infection or renal scarring.
• Renal ultrasonography
• • This study is useful to determine the size and shape of the kidneys, but it is generally poor for visualizing nondilated ureters. Renal ultrasonography does not provide information regarding renal function.
  • Renal ultrasonography has low sensitivity (50%) in detecting APN, though focal abnormalities on sonograms, combined with a CRP level of greater than 70 mg/L may be predictive of renal scarring.
  • Findings on power Doppler ultrasonography were recently correlated with DMSA findings of APN.
  • A renal sonogram is useful in the diagnosis of urolithiasis, hydronephrosis, hydroureter, ureteroceles, and bladder distention.
• Voiding cystourethrography (VCUG)
• • VCUG is useful for visualizing the urethral and bladder anatomy and for the detecting VUR.
  • VCUG may be performed after 3-4 days of therapy to ensure that bladder irritability has resolved and that the urine is sterilized. VCUG should be performed at the earliest convenient time.
  • The voiding phase is needed to evaluate for VUR and posterior urethral valves.
• Nuclear cystography
• • This study is good for evaluating the bladder and detecting VUR. However, it does not permit adequate evaluation of the urethra and is therefore not used for an initial evaluation of the urologic anatomy.
  • Cystography has only about 1% of radiation dose of fluoroscopic study.
  • Cystography may be used for serial follow-up studies.
• Nuclear cortical scanning
• • Nuclear cortical scanning depicts tubular damage and scarring. It provides information regarding the general size of the kidneys; however, it does not provide detailed information regarding the collecting system. DMSA scanning is not necessary to evaluate or follow up most episodes of APN.
  • This study most frequently involves the use of technetium-99m DMSA to depict renal cortical scarring. The volume of initial defect is useful in predicting the development of renal scars.
  • Follow-up DMSA scans performed more than 6 months after APN resolves are useful to detect permanent renal scarring. Studies performed less than 6 months after APN may show residua of the original infection rather than permanent scars.
  • DMSA scans can help in determining the cause of fever in children with chronic bacteriuria, such as patients with spinal-cord injury and those who undergo clean intermittent catheterization.
  • DMSA as a sensitivity of more than 90% in detecting changes that are suggestive of APN.
  • Radiation exposure to the patient undergoing this procedure is low.
• MRI
• • Gadolinium-enhanced MRIs are correlated with DMSA scans in detecting renal parenchymal defects and is effective in distinguishing acute inflammation from scars.
  • MRI is superior to nuclear scintigraphy in distinguishing acute inflammation from chronic scars.
  • MR cystography may be useful in evaluating VUR.
  • Sedation is generally required. 
• CT: Enhanced CT may be useful in distinguishing APN from other causes of fever.

Procedures

• Patients who cannot provide a midstream, clean-catch urine sample may require catheterization of the bladder or, in neonates, suprapubic bladder aspiration, to obtain the sample.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Routine supportive care includes adequate hydration, analgesia, and use of antipyretics.
• Intravenous (IV) fluid replacement and parenteral antibiotics are indicated for children unable to take medication and fluids orally (PO). IV therapy may be continued until the child can receive PO medication and fluids.
• Septic or toxic patients require hospitalization for treatment.
• Treatment with fluids and PO antibiotics may be given on an outpatient basis if children are not vomiting and not markedly ill.
• The optimal duration of therapy is not well studied, though recommended treatment is in the range of 7-14 days. Some studies have shown that recurrent infection rates increase with short courses of treatment.
• The results of urine cultures ultimately dictate the choice of antibiotics. Because E coli causes more than 95% of all cases of APN in children, initial treatment should be based on regional susceptibility to this pathogen. Because of high resistance rates to amoxicillin, initial treatment should include a cephalosporin (third or fourth generation), amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole (TMP-SMZ), or aminoglycoside.
• • Initial PO therapy with cefixime or amoxicillin-clavulanate is equivalent to IV ceftriaxone for 3 days followed by PO therapy. Rates of renal scarring are equal in children treated PO and IV, though further study is needed to determine whether a subgroup of children with dilating VUR may have high rates of renal scarring if treated with PO antibiotics. Further studies are needed to ensure that currently available antibiotics have the same efficacy.
  • Initial therapy with IV antibiotics for 3-4 days followed by PO therapy to complete a 10-14 day course is equivalent to 10-14 days of IV therapy.
  • A single dose of ceftriaxone given intramuscularly (IM) followed by PO therapy offers no advantage over 10 days of PO therapy alone. Hospitalization is required in similar numbers because of vomiting.
  • IV gentamicin may be dosed daily rather than 3 times a day for children who require IV treatment or who are infected with multiresistant organisms.
  • To the authors' knowledge, recommendations for treatment of infants and children with neurogenic bladder or clinically significant anatomic abnormality have not been studied.

Consultations

Consultations are typically not required at time of presentation.

• A urologist should be consulted for an infant or child with obstruction or a clinically significant anomaly of the urinary tract.
• Consultation with an infectious disease specialist is necessary only if an unusual or resistant organism is identified.
• Consult a nephrologist when patients have impaired renal function.

Diet

In general, no dietary restrictions are necessary.

Activity

No restrictions on activity are needed.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antibiotic therapy should be started after the urinalysis and cultures have been performed. A 7-14-day course of antibiotics is recommended. Special attention is needed when dosing antibiotics in neonates and in infants born prematurely.

Drug Category: Antibiotic agents

Empiric antibiotics should be chosen to cover E coli and Enterococcus, Proteus, and Klebsiella species.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hospitalization is necessary in any of the following situations:
• • Toxicity or sepsis
  • Signs of urinary obstruction or significant underlying disease
  • Inability to tolerate adequate PO fluids or medications
  • Infants and children younger than 2 years with febrile UTI (presumed pyelonephritis)
  • All infants younger than 3 months

Further Outpatient Care

• Patients treated exclusively in the outpatient setting should be followed up in 48 hours to ensure adequate hydration and an appropriate response to therapy.
• After acute treatment is finished, initiate a suppressive dose of an antibiotic until the evaluation for VUR is complete.
• For a first infection, perform renal ultrasonography and VCUG.
• If low-grade VUR is observed (grades I-III), antibiotic prophylaxis may not be required.  Antibiotic prophylaxis should be continued for VUR grades IV and V (see Vesicoureteral Reflux).
• Manage Constipation and Voiding Dysfunction.

In/Out Patient Meds

• Antipyretics
• Analgesic
• Antibiotics

Complications

• Dehydration is the most common acute complication of pyelonephritis. IV fluid replacement is necessary in severe cases.
• APN may lead to renal abscess formation.
• Long-term complications include renal parenchyma scarring, hypertension, decreased renal function, and, in severe cases, renal failure.

Prognosis

• Most cases of pyelonephritis respond readily to antibiotic treatments without further sequelae.
• Permanent renal scars develop in 18-24% of children after APN. Treatment within 5 days from the onset significantly reduces the formation of renal scars.
• For patients with severe cases or chronic infections, appropriate treatment, imaging, and follow-up help prevent long-term sequelae.
• VUR often resolves without permanent damage, provided that patients adhere to prophylactic antimicrobial therapy. Recurrent pyelonephritis in the setting of VUR may be an indication for ureteral reimplantation. Recent studies suggest that antimicrobial therapy may not offer any benefit in preventing recurrent infection. Further research is required to determine the benefits of continuing antibiotic prophylaxis in children with VUR.

Patient Education

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

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• UTI and pyelonephritis must be considered in young pediatric patients with fever and/or nonspecific symptoms so that this fairly common diagnosis is not overlooked.
• It is prudent to order UA and urine cultures in all febrile boys younger than 6 months and febrile girls younger than 24 months, even if a minor potential source of fever, such as gastroenteritis, otitis media, or URI, is present.
• Identification and treatment of APN in the first 5-7 days significantly decreases the risk of renal scarring.

Special Concerns

• Female adolescents who present with symptoms of UTI, pyelonephritis, and/or vaginitis and who are sexually active must be evaluated for pregnancy and sexually transmitted diseases.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• AAP. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics. Apr 1999;103(4 Pt 1):843-52. [Medline].
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• Roilides E, Papachristou F, Gioulekas E, et al. Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99mTc-dimercaptosuccinic acid scans in neonates with urinary tract infections. J Infect Dis. Sep 1999;180(3):904-7. [Medline].
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• Wang YT, Chiu NT, Chen MJ, et al. Correlation of renal ultrasonographic findings with inflammatory volume from dimercaptosuccinic acid renal scans in children with acute pyelonephritis. J Urol. Jan 2005;173(1):190-4; discussion 194. [Medline].
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Article Last Updated: Aug 8, 2007