Ian K. Hewitt

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.

Febrile Urinary Tract Infections in Children

Approximately 7 to 8% of girls and 2% of boys have a UTI during the first 8 years of life. Not all UTIs involve the kidney, but acute pyelonephritis is one of the most common serious bacterial infections in children. This review summarizes diverse views on this topic.

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.

Value of Imaging Studies After a First Febrile Urinary Tract Infection in Young Children: Data From Italian Renal Infection Study 1

OBJECTIVE. We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. METHODS. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children ≤2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. RESULTS. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. CONCLUSIONS. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

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 technetium99dimercaptosuccinic 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 technetium99dimercaptosuccinic 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.

Subclinical rhythmic EEG discharge of adults: SREDA in two children

Subclinical rhythmic electroencephalogram (EEG) discharge is an uncommon rhythmic EEG pattern that has been reported to occur in adults. It is thought to be a nonspecific finding with little clinical significance. This article reports this EEG pattern in two children and suggests it be called subclinical rhythmic EEG discharge of adults and children.

KHA‐CARI guideline: Diagnosis and treatment of urinary tract infection in children

Child & Adolescent Renal Service, Royal Children’s and Mater Children’s Hospitals, University of Queensland, Department of Paediatrics and Child Health, The University of Queensland, Brisbane, Queensland, Department of General Medicine, The Royal Children’s Hospital, Vaccine and Immunisation Research Group and Rotavirus Research Group, Murdoch Childrens Research Institute, Department of Paediatrics, The University of Melbourne, Paediatric Imaging, Monash Health, Monash University, Department of Nephrology, Royal Children’s Hospital Melbourne, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Victoria, Department of Nephrology, Princess Margaret Hospital for Children, Perth, Western Australia, Nephrology, Sydney Children’s Hospital, School of Women’s & Children’s Health, University of New South Wales, and Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia

Pediatric febrile urinary tract infections: the current state of play

Studies undertaken in recent years have improved our understanding regarding the consequences and management of febrile urinary tract infections (UTIs), which are amongst the most common serious bacterial infections in childhood, with renal scarring a frequent outcome.In the past pyelonephritic scarring of the kidney, often associated with vesico-ureteral reflux (reflux nephropathy) was considered a frequent cause of chronic renal insufficiency in children. Increasing recognition as a consequence of improved antenatal ultrasound, that the majority of these children had congenital renal hypo-dysplasia, has resulted in a number of studies examining treatment strategies and outcomes following UTI.In recent years there is a developing consensus regarding the need for a less aggressive therapeutic approach with oral as opposed to intravenous antibiotics, and less invasive investigations, cystourethrography in particular, following an uncomplicated first febrile UTI. There does remain a concern that with this newer approach we may be missing a small subgroup of children more prone to develop severe kidney damage as a consequence of pyelonephritis, and in whom some form of intervention may prove beneficial. These concerns have meant that development of a universally accepted diagnostic protocol remains elusive.

Antibiotic Prophylaxis for Urinary Tract Infection–Related Renal Scarring: A Systematic Review

This literature review and meta-analysis demonstrated antibiotic prophylaxis to be ineffective in the prevention of UTI–related renal scarring in otherwise healthy children. CONTEXT: Acute pyelonephritis may result in renal scarring. Recent prospective studies have shown a small benefit of antibiotic prophylaxis in preventing symptomatic and febrile urinary tract infections (UTIs), while being underpowered to detect any influence in prevention of renal damage. OBJECTIVES: Review of the literature and a meta-analysis to evaluate the effect of antibiotic prophylaxis on UTI-related renal scarring. DATA SOURCES: Medline, Embase, and Cochrane Controlled Trials Register electronic databases were searched for studies published in any language and bibliographies of identified prospective randomized controlled trials (RCTs) performed and published between 1946 and August 2016. STUDY SELECTION: Subjects 18 years of age or younger with symptomatic or febrile UTIs, enrolled in prospective RCTs of antibiotic prophylaxis where 99mTc dimercaptosuccinic acid scans were performed at entry into the study and at late follow-up to detect new scar formation. DATA EXTRACTION: The literature search, study characteristics, inclusion and exclusion criteria, and risk of bias assessment were independently evaluated by 2 authors. RESULTS: Seven RCTs (1427 subjects) were included in the meta-analysis. Our results show no influence of antibiotic prophylaxis in preventing renal scarring (pooled risk ratio, 0.83; 95% confidence interval, 0.55–1.26) as did a subanalysis restricted to those subjects with vesicoureteral reflux (pooled risk ratio, 0.79; 95% confidence interval, 0.51–1.24). LIMITATIONS: Limitations include the small number of studies, short duration of follow-up, and insufficient children with high-grade dilating reflux and/or renal dysplasia enrolled in the studies. CONCLUSIONS: Antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile UTI in otherwise healthy children.

Altered in vitro lymphocyte response in childhood nephrotic syndrome

The immune system, and disturbed T lymphocyte function in particular, has previously been implicated in the pathogenesis of childhood idiopathic nephrotic syndrome. As this disorder is commonly responsive to steroid therapy, we set out to determine whether in vitro suppresion of lymphocyte blastogenic response to the mitogen phytohaemagglutinin (PHA) could predict the clinical situation. Comparing nine nephrotic children with nine healthy controls we were able to show the inhibitory prednisolone dose that suppressed lymphocyte blastogenesis by 50% (ID50) at a known concentration of PHA was significantly greater (P<0.005) for nephrotic individuals. However, the in vitro assay did not reliably predict the clinical response to prednisolone. This study further implicates altered lymphocyte function in the mechanisms underlying idiopathic nephrotic syndrome.