Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children.

AIM: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. METHODS: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. RESULTS: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. CONCLUSION: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking.

Long-term clinical consequences of urinary tract infections during childhood: a review.

UNLABELLED: Kidney scarring related to urinary tract infection in childhood has been considered the cause of serious long-term clinical consequences. This assumption is now debated, as the advent of routine antenatal ultrasound in the 1980s has shown that a consistent part of the changes previously attributed to postinfectious scarring is mainly due to congenital malformations. With the aim of determining what is presently known on the long-term clinical consequences of urinary tract infections (UTIs) in childhood, we performed a review of the literature on the relation between UTIs and blood pressure, renal function, growth and pregnancy-related complications. By searching Medline/PubMed and Embase from 1980 to 2011, we identified 20 cohorts of children from 23 papers. CONCLUSIONS: Renal function: there are no clear data to establish long-term consequences following UTIs during childhood. Most data seem to show that the outcome of renal function can already be delineated at first presentation or in the initial years of follow-up; only 0.4% of children with normal renal function at start presented a decrease during follow-up. Hypertension: there is a low risk, associated with renal damage. Growth and pregnancy-related complications: the few available data seem to exclude a major influence of UTIs.

Febrile urinary tract infections in young children: recommendations for the diagnosis, treatment and follow-up.

UNLABELLED: We report the recommendations for the diagnosis, treatment, imaging evaluation and use of antibiotic prophylaxis in children with the first febrile urinary tract infection, aged 2 months to 3 years. They were prepared by a working group of the Italian Society of Pediatric Nephrology after careful review of the available literature and a consensus decision, when clear evidence was not available. CONCLUSION: These recommendations are endorsed by the Italian Society of Pediatric Nephrology. They can also be a tool of comparison with other existing guidelines in issues in which much controversy still exists.

Different guidelines for imaging after first UTI in febrile infants: yield, cost, and radiation.

OBJECTIVE: To evaluate the yield, economic, and radiation costs of 5 diagnostic algorithms compared with a protocol where all tests are performed (ultrasonography scan, cystography, and late technetium(99)dimercaptosuccinic acid scan) in children after the first febrile urinary tract infections. METHODS: A total of 304 children, 2 to 36 months of age, who completed the diagnostic follow-up (ultrasonography, cystourethrography, and acute and late technetium(99)dimercaptosuccinic acid scans) of a randomized controlled trial (Italian Renal Infection Study 1) were eligible. The guidelines applied to this cohort in a retrospective simulation were: Melbourne Royal Children's Hospital, National Institute of Clinical Excellence (NICE), top down approach, American Academy of Pediatrics (AAP), and Italian Society of Pediatric Nephrology. Primary outcomes were the yield of abnormal tests for each diagnostic protocol; secondary outcomes were the economic and radiation costs. RESULTS: Vesicoureteral reflux (VUR) was identified in 66 (22%) children and a parenchymal scarring was identified in 45 (15%). For detection of VUR (47/66) and scarring (45/45), the top down approach showed the highest sensitivity (76% and 100%, respectively) but also the highest economic and radiation costs (€52 268. 624 mSv). NICE (19/66) and AAP (18/66) had the highest specificities for VUR (90%) and the Italian Society of Pediatric Nephrology had the highest specificity (20/45) for scars (86%). NICE would have been the least costly (€26 838) and AAP would have resulted in the least radiation exposure (42 mSv). CONCLUSIONS: There is no ideal diagnostic protocol following a first febrile urinary tract infection. An aggressive protocol has a high sensitivity for detecting VUR and scarring but carries high financial and radiation costs with questionable benefit.

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.

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.

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].