Febrile Urinary Tract Infection and Vesicoureteral Reflux: Approaches to Management in a Young Child

AUTHORS:
Anika M. Turkiewicz, BS, and John W. Harrington, MD

CITATION:
Turkiewicz AM, Harrington JW. Febrile urinary tract infection and vesicoureteral reflux: approaches to management in a young child. Consultant for Pediatricians. 2015;15(13):113-114.

ABSTRACT: Febrile urinary tract infections (UTIs) are common in children, and an initial UTI predisposes them to additional UTIs, especially in the presence of an anatomic urinary system problem. Vesicoureteral reflux (VUR) is more prevalent in children with febrile UTIs and is caused by a valvular defect or an infection-related blockage. Evaluation may include a voiding cystourethrogram. Therapeutic options for VUR include observation, antibiotic prophylaxis, and surgical intervention, although in recent years a more conservative approach has prevailed.

An 18-month-old girl presented with a recurrent febrile urinary tract infection (UTI) that was resistant to treatment with trimethoprim-sulfamethoxazole (TMP-SMX).

The girl had been diagnosed with her first febrile UTI at 8 months of age after presenting then with a high fever and seizures. At that time, normal kidneys were detected on renal and bladder ultrasonography (RBUS), but a voiding cystourethrogram (VCUG) revealed bilateral vesicoureteral reflux (VUR), grade 5 on the right and grade 3 on the left. The girl was placed on antibiotic prophylaxis with TMP-SMX.

At presentation to us, the girl was treated with a cephalosporin, and her prophylaxis regimen was switched from TMP-SMX to nitrofurantoin. The following month, repeated imaging studies revealed grade 4 VUR with bilateral dilation of each renal pelvis (Figure). Given the high grade of bilateral reflux severity and the unlikelihood of spontaneous resolution, the family was offered surgical intervention. However, they decided to forego surgery, and so the girl remained on antibiotic prophylaxis and will return for a repeat VCUG in another year.

UTI and VUR

Urinary tract infection (UTI) is one of the most common pediatric infections, with febrile UTIs occurring in approximately 5% of children aged 2 to 24 months.¹ High-grade fever of unknown origin in this age group is a strong indicator of a febrile UTI, which can be diagnosed by a positive urine culture and urinalysis.² Children who have an initial UTI are susceptible to additional UTIs, especially when they have an anatomic problem in the urinary system.

Despite that many children who develop a UTI have no further complications, additional evaluation should be conducted after confirming the diagnosis to assess for urinary tract abnormalities. Current recommendations state that febrile infants with a first UTI undergo RBUS.^1,2 If ultrasonography results are normal, care of febrile infants with no localizing source can proceed with close observation and surveillance with repeated urine cultures. VCUG is conducted if the results of RBUS are abnormal, or if the child has a recurrence of febrile UTI.²

Although VUR—the retrograde flow of urine from the bladder into the kidneys—affects approximately 1% of children, it is up to 50% more prevalent in children with febrile UTIs.³ In most cases, primary VUR occurs with a defect in the valve, which prevents urine from flowing back from the bladder to the ureters. Secondary VUR often is caused by infection, with a blockage in the urinary tract forcing urine to flow back to the ureters as a result of the increased pressure.

Evaluation of VUR with VCUG entails inserting a catheter into the bladder and injecting a radiopaque contrast dye to fill the bladder. If VUR is present when the bladder is maximally filled, the dye will flow in a retrograde manner from the bladder into one or both ureters and ascend to the kidney or kidneys.

VUR severity is graded from 1 to 5 based on the amount of urine that flows back into the ureters and kidneys. Grade 1 VUR is when urine flows back into an undilated ureter. Grade 2 is when urine flows back into the renal pelvis and calyces but without dilation. Grade 3 is characterized by mild to moderate dilation of the ureter, renal pelvis, and calyces, with minimal blunting of the fornices. Grade 4 features moderate renal tortuosity and dilation of the renal pelvis and calyces. In grade 5 VUR, gross dilation of the ureter, renal pelvis, and calyces occurs, with a loss of papillary impressions and ureteral tortuosity.

Renal scarring is a concern in children with VUR and subsequent febrile UTIs, and it can occur in all VUR grades, with the risk increasing correspondingly with the grade.¹ Children with grade 3 or 4 VUR are more likely to have recurrent febrile or symptomatic UTIs than are children with grade 1 or 2 VUR.⁴

Management of Pediatric VUR

Therapeutic options for VUR include observation, antibiotic prophylaxis, and surgical intervention. A treatment plan is based on the patient’s reflux grade. Although no consensus exists about the optimal medical management of VUR, the goal is to minimize infections, which can predispose patients to pyelonephritis, renal scarring, and eventually hypertension or end-stage renal disease.

The lower the grade of VUR, the higher the chance that it resolves without medical management. Spontaneous resolution occurs in 80% of grade 1 and 2 reflux cases and 50% of grade 3 cases. Only 20% of grade 4 and 5 reflux cases resolve spontaneously.⁵ Children remain on prophylactic antibiotics while waiting for VUR to resolve and are monitored with ultrasonography every 6 to 9 months for kidney damage or other changes.

The Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) trial recently evaluated the efficacy of antibiotic prophylaxis for preventing UTI recurrence in children with VUR diagnosed after a first or second febrile or symptomatic UTI.⁴ Antibiotic prophylaxis was found to reduce the risk of recurrent UTI by 50% among participants.⁴ However, the isolates of participants who had had a second UTI were found to be 63% resistant with antibiotic prophylaxis and 19% resistant with placebo.⁴ The incidence of renal scarring was not reduced in either the treatment group or placebo group.⁴

Surgical intervention often is required if breakthrough infections occur or in the presence of high-grade VUR. Endoscopic injection of a bulking agent, such as Deflux (dextranomer microspheres in a carrier gel of hyaluronic acid) or Macroplastique (cross-linked polydimethylsiloxane in a carrier gel of polyvinylpyrrolidone) is a more recent option that as many as 80% of parents have been selecting for their children.⁶ Such injections are outpatient procedures used for reflux grades 2 through 4, and they have a reported 68% success rate.⁶

If endoscopic injection is not successful after the first procedure, it can be repeated, or else open surgical ureteral reimplantation can be performed. Although it has a success rate from 88% to 100%, ureteral reimplantation usually is reserved as a last resort for higher VUR grades, in case of breakthrough infection, or where previous treatments have failed.⁵

Over the last 5 years, a significantly more conservative approach to UTIs and VUR has prevailed; however, continued vigilance is required to balance the use of prophylactic antibiotics with the possibility of contributing to bacterial resistance as well as the possibility of organ damage from renal scarring. n

Anika M. Turkiewicz is a recent graduate of the University of Virginia in Charlottesville, Virginia. 

John W. Harrington, MD, is the division director of General Academic Pediatrics at Children’s Hospital of The King’s Daughters and a professor of pediatrics at Eastern Virginia Medical School in Norfolk, Virginia.

References

1. Finnell SM, Carroll AE, Downs SM; American Academy of Pediatrics Subcommittee on Urinary Tract Infection. Technical report: diagnosis and management of an initial UTI in febrile infants and young children. Pediatrics. 2011;128(3):e749-e770.

2. Roberts KB. Revised AAP guideline on UTIs in febrile infants and young children. Am Fam Physician. 2012;86(10):940-946.

3. Chandra M. Reflux nephropathy, urinary tract infection, and voiding disorders. Curr Opin Pediatr. 1995;7(2):164-170.

4. RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014;370(25):2367-2376.

5. Sung J, Skoog S. Surgical management of vesicoureteral reflux in children. Pediatr Nephrol. 2012;27(4):551-561.

6. Bae YD, Park MG, Oh MM, Moon DG. Endoscopic subureteral injection for the treatment of vesicoureteral reflux in children: polydimethylsiloxane (Macroplastique^®) versus dextranomer/hyaluronic acid copolymer (Deflux^®). Korean J Urol. 2010;51(2):128-131.