Urinary tract infection

OVERVIEW: What every practitioner needs to know

Urinary tract infection [UTI] is one of the most common infections in childhood. The diagnosis should be made by culture positivity. Initial therapy should be guided by age of the patient and symptom severity, and should include adequate treatment to assure infection eradication. Evaluation of the urinary tract following UTI remains controversial. The use of prophylaxis to prevent further infection is undergoing reassessment.

Are you sure your patient has a urinary tract infection? What are the typical findings for this disease?

Urinary tract infection (UTI) is one of the most common bacterial infections in childhood, occurring in 7%-8% of girls and 2% of boys by age 9 years.

The signs and symptoms of UTI are age dependent:

NEONATES: non-specific fever, vomiting, apparent abdominal pain, jaundice.

INFANTS AND TODDLERS: fever, vomiting, abdominal pain, dysuria, hematuria.

CHILDREN AND ADOLESCENTS: dysuria, frequency, fever, costovertebral angle (CVA) tenderness, vomiting, abdominal pain, hematuria

What other disease/condition shares some of these symptoms?

Because signs and symptoms are quite broad, other conditions that result in fever, abdominal or flank pain, anorexia, and nausea/vomiting can mimic a UTI.

Viral infections, abdominal conditions such as appendicitis or other intrabdominal/periabdominal bacterial infections, malignancy, urinary tract stone disease, and genitourinary infections can mimic UTI.

What caused this disease to develop at this time?

After the first year of life and into the 6th decade of life, UTI is far more common in females than males (F:M 3-4:1). In the first year of life, UTI is more common in males.

Anatomic conditions can predispose to UTI: stasis or obstruction, posterior urethral valves, bladder or ureteral diverticulum, urinary tract stones, meningomyelocele, vesicoureteral reflux (VUR), and sexual activity.

Some predisposing factors appear to have a genetic component in some families, such as VUR and urinary tract stones.

Certain bacteria have features that facilitate infection, such as E. coli that contain P fimbriae that enhance attachment to the urothelium.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

URINALYSIS: A standard urinalysis is not sensitive or specific enough to reliably predict UTI.

In the neonate, urinalysis is notoriously insensitive, and culture is the only sure way to diagnose a UTI.

In children and adolescents, the most predictive urinalysis-like study is an uncentrifuged urine specimen in which greater than 10 white blood cells/cubic millimeter and bacteria by Gram stain are seen. This combination is 85% sensitive and >99% specific, with a positive likelihood ratio of 85 and negative likelihood ratio of 0.1.

With a urinalysis that shows pyuria and/or bacteriuria, culture is still needed. Culture should be obtained either by a true clean catch in children old enough to follow clean catch directions, by catheterization, or bladder (suprapubic) aspiration in neonates and children 2 years or younger.

The standard definition of a UTI by culture is based on the finding of a single bacterial culture of >100,000 colony-forming units (CFU)/mL. However, if catheterization or aspiration is the means by which urine is obtained, >50,000 CFU/mL of a single organism is considered a UTI. Others have argued that even >1000 CFU/ml of a single organism is a UTI when urine is acquired by aspiration.

Bagging of the patient for collection of urine should not be used.

The use of serum procalcitonin [PCT], c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR] have all been proposed to help differentiate pyelonephritis from cystitis. No definite conclusion can be made about their ability to differentiate.

Would imaging studies be helpful? If so, which ones?

This is one of the most controversial areas in the management of UTI in children.

The 3 types of imaging employed are ultrasound (US), voiding cystourethrogram [VCUG] and renal scintigraphy [RS].

For years the common approach was to perform an US followed by VCUG in all children under the age of 6 years with a febrile UTI, even with the first UTI. Following more study, there does not appear to be any evidence that an US adds to the management of children with UTI except in rare circumstances (prolonged fever, persistent flank pain, conditions associated with urologic abnormalities, and infants).

US does not pick up reflux except in the highest grades and even then not reliably so. US does add to the cost of management, but does not add other risk such as exposure to radiation. Nonetheless, AAP published guidelines recommend a renal, ureter, and bladder US after the first UTI in children aged 2 years or younger. This recommendation is rated a Level C because the evidence is not strong. The NICE guidelines from the United Kingdom recommend US for all children six months of age and younger and in children over 6 months only with “complicated” UTI.

As for VCUG, the approach of obtaining a VCUG with the first UTI is no longer viewed as appropriate. VCUG should be considered if US shows hydronephrosis, dilated ureters, scarring, or other obvious anatomic abnormalities. In children aged 2 years or under with UTI recurrences, a VCUG can be considered.

The use of RS is still not considered routine. RS is considered a more reliable method of ascertaining and following renal scars. The practical utility of this information remains for a practitioner remains unclear.

Confirming the diagnosis

1. Assess the likelihood of a UTI if symptoms fit the condition as noted above. In neonates and babies, consider a UTI if no good explanation for a febrile child.

2. (Recommendation Level A) Obtain a urine specimen before starting therapy. In toilet trained children, a clean catch is acceptable. In neonates and children 2 months to 2 years, urine should be obtained by aspiration or catheterization. Urine should be used for urinalysis AND culture. With pyruia and/or bacteriuria and a culture of > 50,000 CFU/mL of a single organism, then UTI is the diagnosis.

3. Imaging after the diagnosis is confirmed. VCUG should be used only in children where evidence of anatomic abnormality is confirmed, usually by US (hydronephrosis, scarring, dilated ureters) (Level B). Renal/bladder US is recommended even with first UTI by AAP guidelines but with only Level C strength of evidence.

If you are able to confirm that the patient has a urinary tract infection, what treatment should be initiated?

Antibiotic therapy is the appropriate treatment for UTI. If urinalysis shows pyuria and/or bacteriuria and culture is obtained, then antibiotics should be initiated prior to culture results. Culture results should guide continuation of therapy and may guide a change in antibiotics, if appropriate. In children under 2 months of age, IV therapy is still considered the approach of choice. In children 2 months and older, oral antibiotics are recommended unless oral antibiotics cannot be used (e.g., vomiting]. Oral treatment should be provided for 7-14 days, but the level of the recommendation for the length of treatment is not strong. Oral treatment of 3 days or fewer is not recommended. Because vomiting is a common symptom, fluid therapy may be needed at presentation.
One of the biggest recommendation changes is the recommendation to avoid routine use of prophylaxis.
The initial treatment of UTI should depend on the local antimicrobial sensitivity patterns, and eventually on the sensitivity pattern found on culture. The oral route is recommended [as noted above] for children 2 months and older if the oral route can be relied upon. The recommended treatment time is at least 7 days and up to 14 days.
For initial oral antibiotic therapy, 3 classes are recommended (in no specific order): 1. Amoxicillin-clavulanate 20-40 mg/kg/day in 3 divided doses. 2. Trimethoprim (6-12 mg/kg)-sulfamethoxazole (30-60 mg/kg) per day in 2 divided doses, or sulfisoxazole 120-150 mg/kg per day in 4 divided doses. 3. Cephalosporin (oral) multiple options, including cefixime, cephalexin, cefuroxime, cefprozil, cefpodoxime.
If the initial treatment is parenteral, then at least 48 hours of treatment should be considered, with switching to oral therapy after 48 hours or when the oral route can be relied upon to complete at least 7 days of treatment. Initial treatment can be: 1) Cephalosporins- ceftriaxone 75 mg/kg every 24 hours; ceftazidime 100-150 mg/kg per day divided every 8 hours; cefotaxime 150 mg/kg per day divided every 8 hours. 2) Gentamicin 7.5 mg/kg per day divided every 8 hours or tobramycin 5 mg/kg per day divided. 3) Piperacillin 300 mg/kg per day divided every 6-8 hours.
The above recommendations are not necessarily appropriate for children under 2 months of age, and especially not for neonates. For neonates and children under 2 months, initial therapy should be parenteral. The use of sulfa-containing medications for neonates is not recommended. Finally, dosing needs to be altered, especially for neonates and premature babies.

What are the adverse effects associated with each treatment option?

Because a number of different antibiotic classes are recommended, the practitioner should be familiar with the usual adverse effects associated with a given antibiotic class.

What are the possible outcomes of urinary tract infections?

UTI is common. While UTI may recur, the overwhelming majority of children will do well and will not experience long-term consequences from a UTI. With frequent recurrences, imaging may be necessary.

Imaging may uncover an anatomic defect of the kidney or vesicoureteral reflux (VUR).

VUR is graded from 1 to 5, with 1 being minor reflux into the ureter, and 5 being ureteral dilation and dilation of the renal pelvis and renal calyces. Grade 5 is seen in 1% of patients studied, and grade 4 is seen in approximately 5% of patients studied. The approach to VUR is to observe in grades 1 and 2 because the overwhelming majority of patients improve with time. Grades 4 and 5 generally require intervention. Most physicians recommend observation for grade 3 as the initial approach.

Available treatment options for UTI are antibiotics. The risk/benefit ratio is low as the treatment is effective and the side effects low.

What causes this disease and how frequent is it?

Detailed epidemiology:

UTI is common, occurring in 7%-8% of girls and around 2% of boys 9 years of age or younger. There is no seasonal variation.

UTI is an infectious disease. The bacteria involved are typically those found in the gastrointestinal tract, with E. coli most common, followed by Klebsiella, Proteus, and Pseudomonas. Skin pathogens such as Enterococcus and Staphylococcus can also be seen.

Predisposing factors for UTIs are defects of the urinary tract that result in incomplete emptying of the bladder (spinal dysraphism), obstruction to free urine flow, or reflux in the urinary tract. Stone disease, especially if it results in obstruction or slowed flow, can lead to infection, and stones in the urinary tract can be a site for bacterial seeding. Another known condition associated with infection is infrequent emptying of the bladder, with bladder dilation or chronic constipation causing urinary retention.

The majority of patients do not have the conditions enumerated above. Whether certain patients have urothelium that is more at risk for bacterial invasion is a speculation. Certain bacteria contain adhesion properties that increase the likelihood of invasion.
There appears to be some genetic predisposition for UTI, with a higher likelihood of urinary tract infection in girls of mothers with a history of UTI. There also appears to be a higher likelihood of the sibling of a patient with VUR also having VUR.

How do these pathogens/genes/exposures cause the disease?

N/A

Other clinical manifestations that might help with diagnosis and management

N/A

What complications might you expect from the disease or treatment of the disease?

The belief that UTI could result in long-term renal scarring, in turn leading to hypertension, chronic kidney disease and even end-stage kidney failure, lead to aggressive imaging and prophylaxis for children, especially those with VUR. With more time, it is clear that the vast majority of patients are not at risk for end-stage kidney disease.

Further, there does not appear to be an advantage to the use of prophylaxis in the vast majority of patients. A recent, long term follow up [2 years] of a large cohort of children with vesicoureteral reflux found prophylaxis did reduce recurrence risk, increased resistance of E coli to a first line medication and did not decrease the risk of scarring.

Thus, with most patients, the major complications are associated with the acute illness, such as missing school with a febrile UTI.

A very small number of patients may experience complications associated with antibiotics.

A small number of patients may develop pyelonephritis with a more extended illness or, even less commonly, septicemia. Septicemia is a larger issue in neonates and helps explain the recommendation for parenteral treatment in neonates and children under 2 months of age.

Are additional laboratory studies available; even some that are not widely available?

N/A

How can urinary tract infections be prevented?

As noted above, prophylaxis is no longer recommended for the vast majority of patients. In patients with high grade reflux, prophylaxis may still be appropriate. The newer recommendation (Level C) is that suspected recurrences of UTI should be evaluated quickly and treated rapidly.

For children with urinary retention, but without muscle or neurologic disease, a regimen of timed bladder emptying is a commonly used approach. In children with chronic constipation, treatment of the constipation and chronic prevention of constipation will reduce UTI recurrence.

Genetic counseling is not applicable to urinary tract infections.

The most commonly asked question regarding UTI and nutrition relates to the use of cranberry juice. There appears to be some benefit to the use of cranberry juice for adult women with UTI, but no direct evidence of benefit for children.

What is the evidence?

“Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months”. Pediatrics . vol. 128. 2011. pp. 595-610. Other sources that were used for recommendations include:

Bloomfield, P, Hodson, EM, Craig, JC. “Antibiotics for acute pyelonephritis in children”. Cochrane Database Syst Rev 2005:CD003772.Cochrane Database Syst Rev. 2015 Jan 20. pp. CD 009185

Montini, G, Tullus, K, Hewitt, I. “Febrile urinary tract infections in children”. New Engl J Med . vol. 365. 2011. pp. 239-50.

Sheikh, N, Borrell, Jl, Evron, J, Leeflang, MM. “Procalcitonin, C-reactive protein and erythrocyte sedimentation rate in the diagnosis of acute pyelonephritis in children”.

“The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract infections”. Expert Rev Anti Infect Ther. vol. 13. 2015 Jan. pp. 81-90.

“The RIVUR Trial Investigators. Antimicrobial Therapy for Children with Vesicoureteral Reflux”. N Engl J Med . vol. 370. 2014. pp. 2367-2376.

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