Treatment and prophylaxis of UTIs: Commentary on current controversies, part 1

Issue: July 2011

Children get urinary tract infections, and there is no controversy that a child with a febrile, symptomatic urinary tract infection requires therapy.

John Bradley, MD

However, to generalize treatment and prophylaxis recommendations without concern for risk factors for renal injury — including upper- vs. lower-tract infection, normal vs. abnormal urinary tract anatomy, vesicoureteral reflux (VUR), and degree of reflux vs. no reflux — creates oversimplification, leading to over-treatment in some and under-treatment in others. Our primary objective is to prevent long-term, cumulative injury to the kidney from recurrent infections that may ultimately result in renal failure and a need for renal transplantation.

As with many of the infections we treat, we just don’t have all the facts with respect to the natural history of the damage to the kidney, either in the short term or over a period of years. Investigators have looked at different populations of children with varying clinical presentations, using different techniques to assess injury. As one might expect, it is almost impossible to define different renal-injury risk groups of children, assign them a treatment (or prophylaxis) regimen, compared with placebo, and follow them for 10 years on the same regimen, with no “exceptions to protocol therapy” to assess which protocol is more effective. A 2011 Cochrane Review on long-term antibiotic prophylaxis in children highlighted the problem of “pooling” data from various published studies, as the duration of prophylaxis, antibiotics used, populations evaluated, endpoints measured, etc., were varied from one study to the next.

Another recent systematic review of the published literature by Shaikh and colleagues suggests that of all children who present with a urinary tract infection (UTI), 57% will have evidence of upper-tract kidney infection (by DMSA radionuclide scan), and 15% will have evidence of renal scars after their first infection (also assessed by DMSA scan). They also shared information from the investigators who studied these children, in which pyelonephritis was more likely to occur in children with VUR (which is logical), and even more importantly, that the degree of reflux correlated well with the risk for developing renal scars as a consequence of infection (the greater the reflux, the greater the risk of scars; also logical). These data are essential because they help define the different risks for various subgroups of children, so that we can assess whether the potential benefit of long-term antibiotic exposure is justified for each subgroup. Although we may find that the benefits may justify the risks of long-term antibiotic exposure in a child with massive, grade 5 reflux and pre-existing renal damage, we need to know if the same is true for the child with no reflux or grades 1 to 2 reflux. For a small clinical benefit (even if ultimately shown to be statistically significant), the practitioner and family may reasonably choose to forgo prophylaxis and just treat each recurrent infection.

Why certain children get UTIs is still not well understood, particularly for the child with no underlying anatomic defect or reflux. However, for those born with a variety of urinary tract anomalies, from duplicated kidneys and collecting systems, to posterior urethral valves, to profound anomalies of the urogenital tract and rectum, the flow of urine emerging into the renal pelvis to the distal urethra is clearly altered, allowing the occasional enteric bacillus that ascends into the bladder a favorable environment for growth. More subtle is the issue of risk for recurrent infection based on reflux (grades 1-5), with most investigators believing that grade 3 and greater reflux enhances the risk for recurrent upper-tract disease and scar formation, as noted above.

Most studies evaluating reflux have focused on children with a documented UTI, evaluating these children for reflux. However, large-scale studies to define the prevalence of reflux in normal healthy children (eg, what percent have asymptomatic grade 1-3 reflux) would be helpful. However, the radiation risk inherent in screening 1,000 children and following them for years has not been shown to be justifiable.

Having defined that infections are bad for the kidney, in next month’s editorial I will explore the treatment of infections, and even more importantly for the long-term health of the kidney and the child, the prevention of infections.

For more information:

Craig JC. N Engl J Med. 2009;361:1748-1759.

Hoberman A. N Engl J Med. 2009;361:1804-1806.

Hoberman A. Pediatrics. 1999;104(1 Pt1):79-86.

Pennesi M. Pediatrics. 2008;121:e1489-1494.

RIVUR Study Online Posting. Available at: clinicaltrials.gov/ct2/show/NCT00405704?term=rivur&rank=1.

Shaikh N. Pediatrics. 2010;126:1084-1091.

Williams G. Cochrane Database Syst Rev. 2011;3:CD001534.

John S. Bradley, MD, is director of the division of infectious diseases at Rady Children’s Hospital in San Diego and associate clinical professor of pediatrics at the University of California San Diego. He is also a member of the Infectious Diseases in Children Editorial Board. Disclosure: Dr. Bradley reports no relevant financial disclosures.

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