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Three Part Question

In an [asymptomatic infant or preschool child under 4 years of age] does [the detection and management of asymptomatic bacteriuria (ABU) on routine urine culture] decrease [the incidence of symptomatic UTI or renal scarring]?

Clinical Scenario

An asymptomatic 18-month-old boy, undergoing radiological investigations after a urinary tract infection (UTI) diagnosed a few months earlier, is reviewed at the clinic. According to departmental protocol, a 3-monthly urine culture should be submitted in infants and young children as, until the age of 4 years, they remain at risk of developing renal scars after UTIs. You wonder as to the value of this routine culture.

Search Strategy

PubMed (1975-2003)
("urine culture" OR "asymptomatic bacteriuria" OR "urinary tract infection") AND ("prognosis" OR "renal scar"). Limits- child < 4 years.
Secondary sources- Cochrane Library (Issue 3, 2003): search words –(1: "urine culture" OR 2: "asymptomatic bacteriuria" OR 3: "urinary tract infection. Database of systematic reviews: 32, 24 and 135 articles (for 1,2 and 3 respectively), with 24, 14 and 101 complete reviews (for 1,2 and 3 respectively) No relevant systematic review for under 4.
SumSearch – 43 articles, 2 relevant (already retrieved by PubMed).

Search Outcome

Pubmed search outcome: 12 papers, of which 2 were relevant (under 4 years of age)

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Wettergren et al 1990	Unselected population of 50 patients (14 girls) under 1 year of age with bacteriuria on screening, verified by suprapubic aspiration and untreated. Follow up for up to 6 years.	Prospective cohort (4)	Subsequent periodical urine cultures during the follow up period.	Two infants developed pyelonephritis within 2 weeks of diagnosis of ABU. ABU recurred in 10 children. *	Unselected population of well infants (not after acute UTI). Screening of bacteriuria primarily detected innocent bacteriuria and was not recommended.
			Measurement of renal parenchymal thickness and renal surface area on IVU at 3 years.	No child (0/36) developed new renal damage. IR=0 (95%CI= 0 to 0.09) *
Randolph et al 1975	25 girls under 6 months of age with bacteriuria, followed up with cultures up to 6 years of age. No chemoprophylaxis but treatment of individual episodes.	Prospective cohort (4)	Development of UTI and renal scarring (IVU) during the follow up period.	Although described as ABU, initial episodes were always symptomatic (lower tract symptoms). No scars on initial IVU. Recurrences in 9 infants, always aymptomatic (lower tract symptoms). New scarring developed in 3 children, all of whom had recurrences (symptomatic) and evidence of reflux, bladder trabeculation and urethral stricture. No recurrences after 3 years of age and no new scars at 6 years.	Study exclusively in girls, natural history in boys may be different. Even in ABU, signs of lower UTI were evident to the "instructed parents" .

Comment(s)

* In view of study design (prospective cohort), risk reduction and NNT could not be calculated. As infants and young children are thought to remain at risk, until the age of 4 years, of developing renal scars after UTIs, some paediatric departments carry out periodical urine culture in this group, even in the absence of symptoms. In addition to the fact that urine collection and culture in preschool children under 4 years of age is not always technically easy and is associated with an unsatisfactory high risk of bacterial contamination, detection of ABU in this group would be of value if its treatment results in decreased risk of renal scarring and symptomatic UTI, without adverse effects of the therapy. Previous reports have shown that the development of new renal scars or the progression of existing scars are very uncommon after the age of 4 years (Vernon et al), and, although new scars may occasionnaly develop after the age of 4 years, they generally occur in the context of symptomatic UTI or acute pyelonephritis but not after ABU (Wennerstrom et al). Although there is evidence of progression of scarring in relation to ABU, there is no evidence of benefit from treatment. Studies of ABU in school children have shown that absence of treatment does not increase the risk of subsequent renal scarring after the age of 5 years (Cardiff/Oxford group) and that bacterial strains in ABU do not commonly cause symptomatic pyelonephritis (Lindberg). However, changes in bacterial flora have been associated to recurrences of or development of acute pyelonephritis ABU (Olling et al). In children with ABU, the use of antibiotherapy for intercurrent infections leads to a change in the urinary flora and is associated with an increased risk of pyelonephritis (Hansson et al), in contrast to untreated ABU where no spontaneous changes of urinary bacteria occurs (Hansson et al). We therefore reviewed all published studies to try answering specifically the structured clinical question: what is the evidence that the detection and management of ABU in preschool children under 4 years of age decrease the incidence of symptomatic UTI or renal scarring? Unfortunately, we found no good quality randomised studies addressing that specific question. The 2 studies reviewed show that, in children under 4, no new renal scarring occurred when bacteriuria was asymptomatic (Wettergren) and that renal scarring only occurred in children with symptomatic recurrences associated with abnormal cystograms (Randolph). However, both studies have obvious weaknesses: in addition to small sample sizes, there was no treatment randomisation. The first study was carried out in an unselected population of children, but not after a selected group with previous UTI which would very likely have a different natural history and prognosis. The second study was carried out exclusively in girls, who are known to have a different natural history than boys. In addition, as these studies were carried out before DMSA was available, the diagnosis of renal damage was made by IVU. As DMSA is more sensitive than IVU to detect cortical scarring, some small scars may not have been recognised on IVU, although such small scars are not thought to be clinically significant. In addition, the first study did not clearly differentiate between primary and secondary (after a previous UTI) ABU. Despite their weaknesses, which should caution about the generalisation of their findings, these studies have shown that the detection and the treatment of ABU in infants and preschool children did not decrease the risk of renal scarring. In addition, antibiotic-induced modifications of the bacterial flora may increase the risk of acute pyelonephritis, and therefore the risk of cortical damage. Therefore, the practice of routine detection of bacteriuria in asymptomatic infants and preschool children is not supported by evidence in the table and may even be harmful (Olling, Hansson). Future randomised double-blinded controlled studies, clearly differentiating between primary and secondary ABU, with outcomes based on DMSA, are recommended.

Clinical Bottom Line

There is no evidence to show that detection and treatment of ABU in infants and preschool children decrease the risk of renal scarring. The benefit of routine detection and treatment of ABU in such children is not supported by evidence and may even be harmful.

References

1. Wettergren B, Hellström M, Stokland E, Jodal U. Six year follow up of infants with bacteriuria on screening. BMJ 1990;301:845-8.
2. Randolph MF, Morris KE, Gould EB. The first urinary tract infection in the female infant. Prevalence, recurrence, and prognosis: a 10-year study in private practice. J Pediatr 1975;86(3):342-8.
3. Vernon SJ, Coulthard MG, Lambert HJ, Keir MJ, Matthews JN New renal scarring in children who at age 3 and 4 years had had normal scans with dimercaptosuccinic acid: follow up study. BMJ 1997;315:905-8.
4. Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J.Pediatr 2000;136:30-4.
5. Cardiff-Oxford bacteriuria Study Group. Sequelae of covert bacteriuria in schoolgirls. A four-year follow-up study. Lancet 1978;1 :889-93.
6. Lindberg U. Asymptomatic bacteriuria in school girls. V. The clinical course and response to treatment. Acta Paediatr.Scand. 1975;64:718-24.
7. Olling S, Jones KV, Mackenzie R, Jones ER, Hanson LA, Asscher AW. A four-year follow-up of schoolgirls with untreated covert bacteriuria: bacteriological aspects. Clin.Nephrol. 1981; 16:169-71.
8. Hansson S, Jodal U, Lincoln K, Svanborg-Eden C. Untreated asymptomatic bacteriuria in girls: II--Effect of phenoxymethylpenicillin and erythromycin given for intercurrent infections. BMJ 1989;298:856-9.
9. Hansson S, Caugant D, Jodal U, Svanborg-Eden C. Untreated asymptomatic bacteriuria in girls: I--Stability of urinary isolates. BMJ 1989;298:853-5.