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Fosfomycin, originally named phosphonomycin when it was first isolated from fermentation broth of Streptomyces species and synthesized at Merck in 1969. The phosphonic acid containing a structurally strained and reactive epoxide ring confers broad spectrum, bactericidal activity against gram-positive and gram-negative bacteria. Fosfomycin's small size and hydrophilicity permits broad tissues penetration. Although only fosfomycin tromethamine oral is approved for urinary tract infections (UTI) in the United States since 1996, the intravenous form has been utilized worldwide for over four decades. The increasing rates of multidrug-resistant (MDR) infections with few novel treatment options available has spurred the recent interest in fosfomycin. Fosfomycin's high urinary concentration, broad spectrum of activity against MDR pathogens, and favorable safety profile offers a valuable oral option for treating UTI, one of the most common bacterial infections in childhood. The ability of fosfomycin to penetrate biofilm and reported activity against intracellular pathogens may further its importance in childhood diseases such as Chronic Granulomatous Disease, Salmonellosis, and Listeriosis. More data are needed to further define optimal Pharmacodynamic target, as well as Pharmacokinetic, safety and outcomes for repeated oral and intravenous dosing of fosfomycin in infants and children in systemic infections., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk. [ABSTRACT FROM AUTHOR]

Vesico-ureteral reflux (VUR) has long been recognized as associated with urinary tract infections (UTIs), renal scarring, and chronic kidney disease (CKD). The concept of "reflux nephropathy" was born, whereby the VUR was considered the culprit, predisposing to recurrent UTIs and providing a conduit whereby the infection could ascend to the kidneys resulting in scarring and destruction. The more severe grades of reflux were thought to place the young child at particular risk of CKD. The question being asked in this pro/con debate is whether VUR is indeed the culprit responsible for a significant proportion of children with CKD, a number of whom progress to end-stage kidney failure (ESKF), and is thus important to find and treat, or is it an innocent bystander associated with CKD and ESKF but not the cause. We believe the latter and will present convincing evidence supported by large scale prospective randomized controlled trials that VUR is not the ogre it was thought to be and is not important to find following a UTI (with some exceptions). [ABSTRACT FROM AUTHOR]

Background: The conclusion drawn by the authors of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial is that antimicrobial prophylaxis reduces the risk of recurrent urinary tract infection (UTI)-but not of renal scarring-in patients with vesicoureteral reflux (VUR). Results: A review of the findings showed that the decreased recurrent UTI rate was only present at the end of the 2-year follow-up period and was only slightly increased (12.3 %) above the 10 % cutoff for statistical significance. The difference was not observed in children younger than two years of age with VUR grade III and IV. In addition, the rate of new renal scarring was not statistically different between the prophylaxis and placebo groups (8.2 vs. 8.4 %, respectively). A high rate of uropathogen antibiotic resistance was observed in the prophylaxis group (68.4 vs. 24.6 %, respectively). Conclusion: The analysis of the RIVUR findings questions the validity of its authors suggestion that the results may warrant reconsideration of the current recommendations by the American Academy of Pediatrics on obtaining a voiding cystourethrogram after the first febrile UTI and the use of urinary antibiotic prophylaxis in VUR patients. [ABSTRACT FROM AUTHOR]

Vesicoureteral reflux (VUR) increases the risk of urinary tract infection (UTI) and renal scarring. Many prospective studies have evaluated the role of antimicrobial prophylaxis in the prevention of recurrent UTI and renal scarring in children with VUR. Of these, the RIVUR trial was the largest, randomized, placebo-controlled, double blind, multicenter study, involving 607 children aged 2-72 months with grade I-IV VUR and a first or second symptomatic UTI. The median age of children in the RIVUR trial was 12 months, 92 % were female, 91 % were randomized after a first UTI, 86 % had a febrile index UTI, and 71 (56 %) of 126 toilet-trained children had bladder bowel dysfunction. Trimethoprim/sulfamethoxazole reduced the risk of UTI recurrences by 50 % (hazard ratio 0.50; 95 % confidence interval 0.34-0.74) as compared to placebo. No significant difference was seen in renal scarring between the two groups. However, this does not invalidate the role of prophylaxis in preventing renal scars because RIVUR and other recent prospective studies were not designed to address renal scarring as a primary study endpoint. In view of the RIVUR Trial and other studies that showed similar results, albeit in selected groups of patients, the debate on antimicrobial prophylaxis should shift from 'no prophylaxis' to 'selective prophylaxis' in children with VUR. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) affects about 2 % of boys and 8 % of girls during the first 6 years of life with Escherichia coli as the predominant pathogen. Symptomatic UTI causes discomfort and distress, and carries a risk of inducing renal damage. The strong correlation between febrile UTI, dilating vesicoureteral reflux (VUR), and renal scarring led to the introduction of antibiotic prophylaxis for children with VUR to reduce the rate of UTI recurrence. It became common practice to use prophylaxis for children with VUR and other urinary tract abnormalities. This policy has been challenged because of a lack of scientific support. Now, randomized controlled studies are available that compare prophylaxis to no treatment or placebo. They show that children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. Dilating VUR may still be an indication for prophylaxis in young children. After the first year of life, boys have very few recurrences and do not benefit from prophylaxis. Girls with dilating VUR, on the other hand, are more prone to recurrences and benefit from prophylaxis. There has been a decline in the use of prophylaxis due to questioning of its efficacy, increasing bacterial resistance, and a propensity to low adherence to medication. Alternative measures to reduce UTI recurrences should be emphasized. However, in selected patients carefully followed, prophylaxis can protect from recurrent UTI and long-term sequelae. Key summary points: 1. There is a strong correlation between UTI, VUR, and renal scarring. 2. Children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. 3. Young children, mainly girls, with dilating VUR are at risk of recurrent UTI and acquired renal scarring and seem to gain from antibiotic prophylaxis. 4. Increasing bacterial resistance and low adherence with prescribed medication is a major obstacle to successful antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) is a common thrombotic microangiopathy (TMA) in which central nervous system (CNS) involvement is responsible for the majority of deaths and for severe long-term sequelae. We have analyzed the role of hemoconcentration in disease severity. Methods: This was a retrospective review of the records and laboratory data at presentation of all patients with STEC-HUS cases ( n = 61) over a 10-year period. The patients were grouped into three severity classes: group A, comprising patients who did not require dialysis; group B, patients who were dialyzed without CNS involvement; group C, patients with CNS involvement. Results: Patients with CNS involvement (group C) had a higher mean hemoglobin level (11.2 ± 2.3 g/dL) than those of group A or B ( 9.4 ± 2.1 and 7.5 ± 1.9 g/dL, respectively; p < 0.0001). We also observed that the higher the initial hemoglobin level, the more severe the long-term renal damage ( p < 0.007). Conclusions: In patients with STEC-HUS, hemoconcentration and hypovolemia may be responsible for more severe ischemic organ damage (both short and long term) at disease onset, and these signs should be regarded as risk factors for CNS damage and for more severe TMA. Therefore, we recommend that hydration status should be actively monitored in HUS patients and that dehydration, when diagnosed, should be promptly corrected. [ABSTRACT FROM AUTHOR]

Purpose To compare intravoxel incoherent motion diffusion weight imaging IVIM-DWI MRI with DMSA for the evaluation of cortical defect in pediatric upper urinary tract infection (UTI) patients. Materials and Methods Forty-three kidneys of 22 pediatric patients with the first episode of febrile upper UTI were evaluated. DWI using IVIM model was performed with eight b factors. The presence of cortical defect was evaluated on apparent diffusion coefficient (ADC) map. DMSA was used as the standard of reference. ADC, true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (F) in both defect and nondefect area were calculated and compared. Results Cortical defects were detected in 14 kidneys by IVIM-DWI. The sensitivity, specificity, positive predictive value, and negative predictive value of IVIM-DWI MRI for the detection of defects was 93.3%, 100%, 100%, and 96.5%, respectively. Mean values of ADC, D, D*, and F were 1.12 ± 0.15, 1.05 ± 0.10, 33 ± 17 (× 10−3 mm2/s), and 0.14 ± 0.09 in the defect foci. In normal foci, ADC, D, D*, and F were 1.37 ± 0.09, 1.31 ± 0.10, 43 ± 19 (× 10−3 mm2/s), and 0.12 ± 0.04, respectively. ADC and D were significantly lower in defect group than nondefect group ( P < 0.01). Conclusion IVIM-DWI can allow both direct visualization and quantitative measurement of cortical defects. J. Magn. Reson. Imaging 2014;40:545-551. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Although the diagnosis of vesicoureteral reflux and of reflux nephropathy is a well-established and shared procedure, its treatment nowadays is still very controversial. New developments on the knowledge of pathophysiology of renal damage associated to reflux opened the way towards a different diagnostic work-up and different therapeutic approaches. Recently, the "top-down" diagnostic approach has gained wider interest, versus the "down-top" protocol. The attention has recently focused on the renal parenchyma damage and less interest has been given to the presence and the radiological degree of vesicoureteral reflux. The review criteria were based on an in-depth search of references conducted on PubMed, using the terms "vesicoureteral reflux", "children", "incidence", "etiology", "diagnosis", "treatment" and "outcomes". The selection of the papers cited in this review was influenced by the content and the relevance to the points focused in the article. Conservative approaches include no treatment option with watchful waiting, long-term antibiotic prophylaxis and bladder rehabilitation. The operative treatment consists of endoscopic, open, laparoscopic and robotic procedures to stop the refluxing ureter . No final consensus has been achieved in literature yet, and further studies are necessary in order to better define the subset of children at risk of developing progression of renal damage. This review aims to clarify the diagnostic management and the urological-nephrological treatment of reflux in pediatric age, on the basis of a review of the best-published evidence. [ABSTRACT FROM AUTHOR]

Background: The indications for partial or total nephrectomy for urological reasons are not clearly documented in the paediatric surgical literature and there are only a limited number of publications on this subject.Purpose: In order to clarify the situation in our centre, we reviewed our own indications for nephrectomy over a 20-year period.Methods: Medical records of patients who underwent nephrectomy for urological and oncological causes between May 1990 and October 2010 at our centre were retrospectively reviewed. Indications for nephrectomy were noted. Renal function was noted for urological cases.Results: A total of 357 nephrectomies were undertaken; out of these, 241 cases were for urological causes and 116 for oncological reasons. The majority of total nephrectomies were performed for multicystic dysplastic kidneys, reflux nephropathy, pelvi-ureteric junction obstruction and dysplasia. Eighty-seven patients exhibited no function at the time of nephrectomy. Of the remainder, 17 had <5% function, 18 had 5-10% function, 5 had 10-15% function and 2 patients had 15-20% function.Conclusions: This is the largest series of nephrectomies in the paediatric surgery literature to date. The majority of nephrectomies were undertaken for urological conditions with relative renal function of <10% and could not have been usefully preserved in situ. We suggest that kidneys with >10% function should not be routinely removed. [ABSTRACT FROM AUTHOR]

This study evaluates the impact of pediatric uninary tract infection (UTI)s on the economy and inpatient healthcare utilization in the USA. A retrospective analysis of patient demographics and hospital economics was performed on children less than 18 years of age admitted with a UTI between 2000 and 2006 using the Healthcare Cost and Utilization Project Kids' Inpatient Database. Our results were stratified as follows. Hospital admissions-nearly 50,000 children/year were admitted with a UTI. Pediatric UTIs represented 1.8% of all pediatric hospitalizations. Seventy-three percent of patients were female and 40% were under 1 year of age. Payer information-from 2000 to 2006, pediatric insurance coverage shifted from the private sector to the public sector. Hospital cost-in 2000, estimated hospital costs for UTIs were $2,858 per hospitalization and rose to $3,838 by 2006. Mean hospital charges increased from $6,279 to $10,489 per stay. By 2006, aggregate hospital charges exceeded $520 million. Our results indicate that UTIs are among the most common pediatric admission diagnoses. Hospitalization is more common in females and younger children. Since 2000, hospital charges for UTIs increased disproportionately to hospital costs. Over time, more children hospitalized with a UTI depend on public agencies to cover healthcare expense. More efforts are needed to evaluate cost-effective strategies for evaluation and treatment of UTIs. [ABSTRACT FROM AUTHOR]

Objective: Urinary tract is one of the most common sources of infection in children under the age of two years. Many known and unknown risk factors predispose to this important disease in children. This study was conducted to determine whether using a specific type of diaper plays a role in urinary tract infection (UTI) in girls under the age of 2 years. Methods: This case control study was performed in hospitalized children; girls with their first urinary tract infection were selected as cases, and those admitted for other reasons comprised the control group. Two groups were matched for age (±1 month), and other known risk factors for UTI. Type of diapers (superabsorbent, standard disposable and washable cotton), used for these children during six months, from October 2007 to March 2008, were compared in both groups. Findings: Fifty-nine matched pair infant girls less than 2 years were selected. It was revealed that in cases with UTI superabsorbent diapers were used more frequently than in controls (Odds ratio =3.29, P-value=0.005) There were no significant differences in other factors like number of diapers used per day, the time between defecation and diaper change, mothers' educational level, level of family income and mother's occupation. Conclusion: The use of superabsorbent diapers could be a risk factor for urinary tract infection in infant girls. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura. DESIGN: Systematic review of randomised controlled trials. SETTING: Secondary and tertiary paediatric and paediatric nephrology services. SUBJECTS: Ten trials involving 1230 children aged less than 18 years. MAIN OUTCOME MEASURES: Persistent proteinuria and/or haematuria. RESULTS: Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14–28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06). CONCLUSIONS: Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) in children appear to be simple and straightforward matters, but there is as yet no consensus on UTIs in this patient group, and it remains one of the most--if not the most--controversial fields in paediatric medicine. Controversy and the lack of consensus can be found in many areas, including the diagnosis and management of UTIs in paediatric patients. Consequently, children with a UTI are investigated and treated quite differently in different parts of the world and also within different parts of the same country. One factor contributing to the current situation is the unexpected difficulty in diagnosing a UTI in children. This difficulty has implications not only for clinical work but also for scientific studies. Substantial over- and under-diagnosing can result from practical difficulties in at least three areas, including problems with collecting urine samples, in interpreting bacterial numbers correctly, and in confusing infantile asymptomatic bacteriuria and a true symptomatic febrile UTI. In this review, these problems will be discussed in detail as well as the implications they have had on clinical practice and research on UTIs. Keywords urine tract infection * bacterial numbers * contamination * asymptomatic bacteriuria, Introduction On the face of it, urinary tract infections (UTI) in children seem to be a simple and straightforward matter, and yet the treatment of UTI is one of the [...]