What are the effects of treatment of acute urinary tract infection in children?

LIKELY TO BE BENEFICIAL

Antibiotics. There is consensus that antibiotics are likely to be beneficial compared with placebo. Placebo-controlled trials of antibiotics for treating children with symptomatic acute urinary tract infection (UTI) are considered unethical.

Oral Antibiotics. One randomized controlled trial (RCT) identified by a systematic review found no significant difference between oral cephalosporins alone and a three-day regimen of intravenous cephalosporins plus continued oral cephalosporins in duration of fever, reinfection rate, renal scarring, or extent of scarring in children two years or younger with a first confirmed UTI. The RCT found weak evidence that in children with grades 3 or 4 reflux, initial intravenous treatment plus oral treatment may reduce renal scarring compared with oral treatment alone at six months.

UNLIKELY TO BE BENEFICIAL

Longer (Seven to 14 Days) Courses of Oral Antibiotics. One systematic review found no significant difference in cure rates between longer courses (seven to 14 days) and shorter courses (two to four days) of the same oral antibiotic seven days after treatment in children with no history of renal tract abnormality and with no acute pyelonephritis diagnosis. Another systematic review also found no significant difference in cure rates between longer and shorter courses of any antibiotic. However, longer courses may be associated with more adverse effects.

Longer (Seven to 14 Days) Courses of Initial Intravenous Antibiotics. One systematic review found no significant difference between long (seven to 14 days) and short (three to four days) courses of initial intravenous antibiotics in persistence of bacteriuria after treatment, recurrent UTI at six to 12 months, or renal scarring at three to six months in children with acute pyelonephritis.

LIKELY TO BE INEFFECTIVE OR HARMFUL

Prolonged Delay in Treatment (Longer than Four Days). We found no RCTs evaluating prolonged delay in treatment. Five retrospective studies found that medium- to long-term delays (four days to seven years) in treatment may be associated with an increased risk of renal scarring.

Single Dose of Oral Antibiotics. One systematic review found that single-dose oral amoxicillin decreased cure rates at three to 30 days compared with a longer (10 days) course of oral amoxicillin. Another systematic review found that single-day or single-dose regimens increased treatment failure compared with seven- to 14-day courses of any antibiotic.

UNKNOWN EFFECTIVENESS

Immediate Empirical Antibiotic Treatment. We found no RCTs comparing early empirical treatment with delayed treatment based on the results of microscopy or culture in children with acute UTI. Retrospective analysis of one RCT found no significant difference in risk of renal scarring 24 hours after cephalosporin treatment compared with 24 hours after the onset of fever in children younger than two years with UTIs.

What are the effects of interventions to prevent recurrence?

LIKELY TO BE BENEFICIAL

Prophylactic Antibiotics. One systematic review found limited evidence that prophylactic antibiotics (a 10-week to 12-month dual regimen of co-trimoxazole and nitrofurantoin) reduced UTI recurrence in children compared with placebo or no treatment. One RCT found that nitrofurantoin reduced recurrence of UTI over six months compared with trimethoprim. However, more children discontinued nitrofurantoin treatment because of adverse effects. We found no RCTs evaluating the optimal duration of prophylactic antibiotics.

Immunotherapy. One RCT that included children with recurrent UTI found that adding pidotimod (an immunotherapeutic agent) to antibiotic treatment reduced recurrence compared with adding placebo.

UNLIKELY TO BE BENEFICIAL

Surgical Correction of Minor Functional Anomalies. We found no RCTs evaluating surgical correction of minor functional anomalies. One observational study suggested that children with minor anomalies do not develop renal scarring and therefore may not benefit from surgery.

Surgical Correction of Moderate to Severe Vesicoureteric Reflux (Grades 3 Through 4) with Adequate Glomerular Filtration Rate. One systematic review showed no significant difference between surgical and medical management (prophylactic antibiotic treatment) of UTIs or their complications after one to five years in children with moderate to severe vesicoureteric reflux, although surgery abolished reflux. One subsequent RCT, reporting at 10-year follow-up, found that new renal scars rarely occurred with either management strategy after five years.

UNKNOWN EFFECTIVENESS

Surgical Correction of Moderate to Severe Vesicoureteric Reflux (Grades 3 Through 4) with Bilateral Nephropathy. One small RCT did not find a significantly greater decline in glomerular filtration rate over 10 years with medical treatment compared with surgery in children with moderate to severe bilateral vesicoureteric reflux and bilateral nephropathy.

Definition

UTI is defined by the presence of a pure bacterial growth of more than 100,000 colony-forming units per mL of urine. 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 usually are considered on the basis of differential risk and different approaches to management: children younger than one year; young children (one to five or seven years, depending on the information source); and older children (12 to 16 years of age). Recurrent UTI is defined as further infection caused by a new organism. Relapsing UTI is defined as further infection caused by the same organism.

Incidence

Boys younger than three months are more susceptible to UTI; thereafter, the incidence rate is substantially higher in girls. Estimates of the true incidence of UTI depend on rates of diagnosis and investigation. At least 8 percent of girls and 2 percent of boys will have a UTI in childhood.¹

Etiology

The normal urinary tract is sterile. Contamination by bowel flora may result in UTI if a virulent organism is involved or if the child is immunosuppressed. In neonates, infection may originate from other sources. Escherichia coli accounts for about 75 percent of all pathogens. Proteus is more common in boys (about 30 percent of infections). Obstructive anomalies are found in up to 4 percent and vesicoureteric reflux in 8 to 40 percent of children being evaluated for their first UTI.² One meta-analysis of 12 cohort studies (537 children admitted to the hospital for UTI, a total of 1,062 kidneys) showed that 36 percent of all kidneys had some scarring on dimercaptosuccinic acid (DMSA) scintigraphy, and that 59 percent of children with vesicoureteric reflux on micturating cystourethrography had at least one scarred kidney (pooled positive likelihood ratio 1.96, 95% confidence interval [CI], 1.51 to 2.54; pooled negative likelihood ratio 0.71, 95% CI, 0.58 to 0.85). There was evidence of heterogeneity in likelihood ratios among studies. The authors concluded that vesicoureteric reflux is a weak predictor of renal damage in children admitted to the hospital.³ Although vesicoureteric reflux is a major risk factor for adverse outcome, other factors, some of which have not yet been identified, also are important. Vesicoureteric reflux runs in families: in one review article, the incidence of reflux in siblings ranged from 26 percent (a cohort of asymptomatic siblings) to 86 percent (siblings with a history of UTI), compared with a rate of less than 1 percent in the normal population.⁴ Although some gene variants appear to be more common in children who have renal damage, no clear link has been established between specific genes and an adverse outcome.⁵ Local or systemic immune problems also are likely to be factors in the development of UTI.

Prognosis

After first infection, about 50 percent of girls have a subsequent UTI within the first year and 75 percent have one within two years.⁶ We found no figures for boys, but a review suggests that recurrences are common in children younger than one year but are rare subsequently.⁷ Renal scarring occurs in 5 to 15 percent of children within one to two years after their first UTI, although 32 to 70 percent of these scars are noted at the time of initial assessment.² The incidence of renal scarring rises with each episode of infection in childhood.⁸ Retrospective analysis of an RCT comparing oral versus intravenous antibiotics found that new renal scarring after a first UTI was more common in children with vesicoureteric reflux than in children without reflux (logistic regression model; 15 percent absolute risk [AR] of scarring with reflux compared with 6 percent without reflux; rate ratio [RR] 2.47, 95% CI, 1.17 to 5.24).⁹ A study (of 287 children with severe vesicoureteric reflux treated medically or surgically for any UTI) evaluated the risk of renal scarring with serial DMSA scintigraphy over five years. The study showed that children younger than two years were at greater risk for renal scarring than older children regardless of treatment (AR for deterioration in DMSA scan over five years: 24 percent for younger children compared with 13 percent for older children; RR 1.82, 95% CI, 1.09 to 3.03).¹⁰ One prospective study found that children of all ages who presented with symptoms of pyelonephritis were likely to have renal abnormalities (abnormal initial scans in 52 percent of children).¹¹ Another prospective study found that the highest rates of renal scarring after pyelonephritis occurred between one and five years of age.¹² A further prospective study by the same team showed that children older than one year had more abnormal DMSA scans three months after an episode of pyelonephritis than younger children (42 percent of older children compared with 24 percent of younger children; RR 1.73, 95% CI, 1.14 to 2.63).¹³ The study noted conflicting results in previous literature on this subject.¹⁴ It also showed that girls were more likely than boys to have scarring on DMSA scan three months after an episode of pyelonephritis (39 percent of girls compared with 18 percent of boys; RR 2.13, 95% CI, 1.15 to 3.96).¹³ Renal scarring is associated with future complications: poor renal growth, recurrent adult pyelonephritis, impaired glomerular function, early hypertension, and end-stage renal failure.^14–17 A combination of recurrent UTI, severe vesicoureteric reflux, and the presence of renal scarring at first presentation is associated with the worst prognosis. One prospective observational study assessed the persistence of scarring on DMSA scans in children with first-time UTI.¹⁸ Grading of scars was as follows: mild (less than 25 percent of kidney affected), moderate (25 to 50 percent of kidney), and severe (greater than 50 percent of kidney). The study found that vesicoureteric reflux was associated with more persistent scarring at six months. Among children with severe scarring on initial scan, 88 percent with reflux had a persisting lesion compared with 14 percent without reflux; RR 6.13, 95% CI, 0.98 to 38. Among children with mild to moderate scarring on initial scan, 38 percent with reflux had a persisting lesion compared with 16 percent without reflux; RR 2.70, 95% CI, 0.81 to 9.10.¹⁸ The study also showed that vesicoureteric reflux was associated with a higher risk of pyelonephritis on the initial scan (RR for pyelonephritis with reflux compared with no reflux 1.62, 95% CI, 1.14 to 2.31).

editor’s note: Co-trimoxazole is called trimethoprim/sulfamethoxazole in the United States. Pidotimod is not available in the United States. [ corrected]

search date: January 2004

Adapted with permission from Larcombe J. Urinary tract infection in children. Clin Evid Concise 2005;13:92–5.