Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.

OBJECTIVES: Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. METHODS: The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. RESULTS: Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. CONCLUSIONS: For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.

Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials.

OBJECTIVES: The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment, given parenterally if necessary. In support of this recommendation, data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited. Because the risk was not well defined, we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children. METHODS: The research findings are derived from 2 multicenter, prospective, randomized, controlled studies, Italian Renal Infection Study 1 and 2, whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis, respectively. From the 2 studies, we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later. The children were 1 month to <7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy. RESULTS: Progressive delay in antibiotic treatment of acute pyelonephritis from <1 to >/=5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later. The risk of scarring remained relatively constant at 30.7 +/- 7%. Clinical and laboratory indices of inflammation were comparable in all groups, as was the incidence of vesicoureteric reflux. CONCLUSIONS: Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring. Furthermore, there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with older children.

Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial.

OBJECTIVE: To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. DESIGN: Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. SETTING: 28 paediatric units in north east Italy. PARTICIPANTS: 502 children aged 1 month to <7 years with clinical pyelonephritis. INTERVENTION: Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37 degrees C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. RESULTS: Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk -4%, 95% confidence interval -11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (-0.9 to 6.0); white cell count 9.8x10(9)/l (SD 3.5) v 9.5x10(9)/l (SD 3.1), mean difference 0.3 (-0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference -0.05% (-1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. CONCLUSIONS: Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. TRIAL REGISTRATION: Clinical Trials NCT00161330 [ClinicalTrials.gov].