Clinical review

Urinary tract infection in children

James Larcombe, general practitioner. 

Sedgefield, County Durham TS21 3BN

Jhlarcombe{at}aol.com

This review of the effects of treatment for urinary tract infection in children and of preventive interventions is one of over 60 chapters in the first issue of Clinical Evidence, published by the BMJ Publishing Group.

	Background

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Definition: Urinary tract infection is defined by the presence of a pure bacterial growth >10⁵ colony forming units/ml. Lower counts of bacteria may be clinically important, especially in boys and in specimens obtained by urinary catheter. Any growth of typical urinary pathogens is considered clinically important if obtained by suprapubic aspiration. In practice, three age ranges are usually considered on the basis of differential risk and different approaches to management: under 1 year old; young children (1 to 4, 5, or 7 years old, depending on the source); and older children (up to 12-16 years old). Recurrent urinary tract infection is defined as a single further infection by a new organism. Relapsing urinary tract infection is defined as a further infection with the same organism.

Incidence/prevalence: Boys are more susceptible before the age of 3 months; thereafter the incidence is substantially higher in girls. Estimates of the true incidence of urinary tract infection depend on rates of diagnosis and investigation. At least 8% of girls and 2% of boys will have a urinary tract infection in childhood.¹

Aetiology: The normal urinary tract is sterile. Contamination by bowel flora may result in urinary infection if a virulent organism is involved, if the child is immunosuppressed, or both. In neonates, infection may originate from other sources. Escherichia coli accounts for about three quarters of all pathogens. Proteus is more common in boys (around 30% of infections). Obstructive anomalies are found in 0-4% and vesicoureteric reflux in 8-40% of children being investigated for their first urinary tract infection.² Although vesicoureteric reflux is a major risk factor for adverse outcome, it is likely that other as yet unidentified triggers also need to be present.

Prognosis: After first infection, about half of girls have a further infection in the first year and three quarters within two years; we found no figures for boys. Renal scarring occurs in 5-15% of children within one to two years of their first urinary tract infection, although 32-70% of these scars are noted at the time of initial assessment.² The incidence of new renal scars rises with each episode of infection.³ Renal scarring is associated with future complications: poor renal growth, recurrent adult pyelonephritis, impaired glomerular function, early hypertension, and end stage renal failure.^4-6 A combination of recurrent urinary infection, severe vesicoureteric reflux, and the presence of renal scarring at first presentation is associated with the worst prognosis.

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Aims: To relieve acute symptoms, to eliminate infection, and to prevent recurrence, renal damage, and long term complications.

Outcomes: Acute: clinical symptoms (dysuria, frequency, fever); urine culture; incidence of new renal scars. Chronic: incidence of recurrent infection; prevalence of renal scarring; renal size and growth; renal function; prevalence of hypertension and renal failure.

	Methods

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Systematic reviews were extracted from validated searches of Medline, Embase, and the Cochrane database in July 1999. Randomised controlled trials (RCTs) and controlled cohort studies were also identified. We gave priority to studies on the basis of their methodology, relevance, and appicability.

We found little evidence on the effects of delaying treatment while awaiting microscopy or culture results, but retrospective studies suggest that delayed treatment may be associated with increased rates of renal scarring. Placebo controlled trials of antibiotics for symptomatic acute urinary tract infection in children would be considered unethical. One systematic review found that antibiotic treatment for seven days or longer was more effective than short courses.⁷

Benefits
Immediate empirical versus delayed treatment: We found no RCTs comparing immediate empirical treatment versus treatment delayed while awaiting microscopy or culture results. Five retrospective observational studies found increased rates of scarring in children in whom diagnosis was delayed from four days in acute urinary tract infection to seven years where a child presented with chronic non-specific symptoms.²

Harms
The studies did not report comparative harms from long compared with short courses of antibiotics, nor from immediate compared with delayed treatment. Potential harms include the risk of unnecessary or inappropriate antibiotic prescription.

Comment
We found no good evidence from which to predict which children are at high risk of complications after an acute urinary tract infection.⁸    

Benefits
We found no RCTs. One systematic review of 63 descriptive studies found no direct evidence to support the effectiveness of routine diagnostic imaging in children with urinary tract infection.² The quality of studies was generally poor and none included clinically important long term outcome measures.

Harms
The studies reported no evidence on harms. Potential harms include those relating to radiation, invasive procedures, and allergic reactions to contrast media.

Comment
Although the studies showed no benefits overall, subgroups of children at high risk of future morbidity, including those with vesicoureteric reflux, may benefit from early investigation. These children cannot be identified clinically.⁹ One prospective study found that the highest rates of renal scarring after an episode of pyelonephritis occurred between the ages of 1-5 years.¹⁰ Older children with more severe presentations may need careful investigation.    

	Option: Prophylactic antibiotics

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Two small RCTs found that prophylactic antibiotics may prevent recurrent urinary tract infections in children, particularly during the period of prophylaxis. The long term benefits of prophylaxis have not been adequately evaluated, even for children with vesicoureteric reflux.¹¹ The optimum duration of treatment is unknown.

Benefits
Versus no prophylaxis: We found no systematic review. One RCT of 45 children with either first or subsequent acute urinary tract infection compared 10 months of treatment with prophylactic antibiotics versus no treatment.¹² During the 10 month prophylaxis period, recurrent urinary tract infections were reported in none of the children in the intervention group compared with 11 in the control group. Twelve months after stopping prophylactic antibiotics, eight children (32%) in the intervention group compared with 13 (64%) in the control group had had a urinary tract infection. A further double blind crossover trial of 18 girls aged 3-13 years found two episodes of infection in one year in the treatment groups compared with 35 in the control groups (P<0.01).¹³

Harms
Potential harms include those of using antibiotics. In one study, although gut flora were affected by treatment, E coli cultured from rectal swabs from 70% of children remained sensitive to the prophylactic antibiotic (co-trimoxazole).¹⁴

Comment
The decision to stop prophylaxis may be made based on trial periods without treatment or, for children with vesicoureteric reflux, two negative cystograms.⁸ It is not possible to clinically identify children who are at high risk of subsequent urinary tract infections and long term damage.⁸ Routine prophylaxis until the results of investigations are known may therefore be warranted.

	Option: Surgical correction for anomalies obstructing micturition

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We found no good studies evaluating surgical correction.

Benefits
We found no systematic review or RCTs. One small observational study suggested that children with minor anomalies do not develop renal scarring and may therefore not benefit from surgery.¹⁵ Eight of 20 children with moderate degrees of vesicoureteric reflux had renal scars compared with none of the eight children with minor anomalies.

Harms
Potential harms include the usual risks of surgery.

Comment
In the presence of major anomalies the prevention of urinary tract infections is not the prime motive of surgical intervention. Minor anomalies may not be associated with significant morbidity and surgical correction has not been evaluated in such children.

	Option: Surgical correction for vesicoureteric reflux

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One systematic review and a subsequent multicentre RCT found no difference between surgery for vesicoureteric reflux and medical management in preventing recurrence or complications from urinary tract infections.

Benefits
We found one systematic review of studies published before 1989 that included four RCTs (total 830 children) comparing surgical correction of moderate/severe (grades III-V) vesicoureteric obstruction versus medical management (continuous prophylactic antibiotics).¹⁶ Surgery abolished reflux, but there were no significant differences in rates of subsequent urinary tract infections, renal function, incidence of new renal scars, hypertension, or end stage renal failure between groups over a period of six months to five years. A subsequent RCT in 132 children found that the incidence of pyelonephritis was lower in children receiving surgical treatment, but there was also no difference in overall clinical outcome.¹⁷ In another arm of this study, six of 20 renal scars were thought to be associated with postoperative obstruction, which may have negated an otherwise beneficial effect of surgery over medical management.¹⁸

Harms
The review did not mention surgical complications, and none of the individual studies was designed to compare harms.¹⁶ As noted above, postoperative obstruction may negate the benefits of surgery.¹⁸

Comment
Better results were obtained by centres handling the greatest number of cases.¹⁹ Surgery is usually considered only in children with more severe vesicoureteric reflux (grade III-V), who are less likely to experience spontaneous resolution.²⁰

	Acknowledgments

Competing interests: None declared.

	References

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1.	Stark H. Urinary tract infections in girls: the cost-effectiveness of currently recommended investigative routines. Pediatr Nephrol 1997; 11: 174-177[Medline].
2.	Dick PT, Feldman W. Routine diagnostic imaging for childhood urinary tract infections: a systematic overview. J Pediatr 1996; 128: 15-22[Medline].
3.	Jodal U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am 1987; 1: 713-729[Medline].
4.	Berg UB. Long-term follow-up of renal morphology and function in children with recurrent pyelonephritis. J Urol 1992; 148: 1715-1720[Medline].
5.	Martinell J, Claeson I, Lidin-Janson G, Jodal U. Urinary infection, reflux and renal scarring in females continuously followed for 13-38 years. Paediatr Nephrol 1995; 9: 131-136[Medline].
6.	Jacobson S, Eklof O, Erikkson CG, Lins LE, Tidgren B. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow-up. BMJ 1989; 299: 703-706.
7.	Moffatt M, Embree J, Grimm P, Law B. Short-course antibiotic therapy for urinary tract infections in children: a methodological review of the literature. Am J Dis Child 1988; 142: 57-61[Abstract].
8.	Greenfield SP, Ng M, Gran J. Experience with vesicoureteric reflux in children: clinical characteristics. J Urol 1997; 158: 574-577[Medline].
9.	Smellie JM, Normand ICS, Katz G. Children with urinary infection: a comparison of those with and those without vesicoureteric reflux. Kidney Int 1981; 20: 717-722[Medline].
10.	Benador D, Benador N, Slozman D, Mermillod B, Girardin E. Are younger patients at higher risk of renal sequelae after pyelonephritis? Lancet 1997; 349: 17-19[Medline].
11.	Garin EH, Campos A, Homsy Y. Primary vesico-ureteral reflux: a review of current concepts. Pediatr Nephrol 1998; 12: 249-256[Medline].
12.	Smellie JM, Katz G, Gruneberg RN. Controlled trial of prophylactic treatment in childhood urinary tract infection. Lancet 1978; ii: 175-178.
13.	Lohr JA, Nunley DH, Howards SS, Ford RF. Prevention of recurrent urinary tract infections in girls. Pediatrics 1977; 59: 562-565[Abstract/Free Full Text].
14.	Smellie JM, Gruneberg RN, Leakey A, Atkin WS. Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: clinical aspects/bacteriological aspects. BMJ 1976; ii: 203-208.
15.	Pylkannen J, Vilska J, Koskimies O. The value of childhood urinary tract infection in predicting renal injury. Acta Paediatr Scand 1981; 70: 879-883[Medline].
16.	Shanon A, Feldman W. Methodological limitations in the literature on vesicoureteric reflux: a critical review. J Pediatr 1990; 117: 171-178[Medline].
17.	Weiss R, Duckett J, Spitzer A. Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesico-ureteral reflux (United States): the international reflux study in children. J Urol 1992; 148: 1667-1673[Medline].
18.	Smellie JM, Tamminen-Mobius T, Olbing H, Claesson I, Wikstad I, Jodal U, et al. Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings: the international reflux study in children. Pediatr Nephrol 1992; 6: 223-220[Medline].
19.	Smellie JM. Commentary: management of children with severe vesicoureteral reflux. J Urol 1992; 148: 1676-1678[Medline].
20.	Sciagra R, Materassi M, Rossi V, Ienuso R, Danti A, La Cava G. Alternative approaches to the prognostic stratification of mild to moderate primary vesicoureteral reflux in children. J Urol (Paris) 1996; 155: 2052-2056.