Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial. Antimicrobial prophylaxis in children with urinary tract infection and vesicoureteral reflux. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring. The Swedish reflux trial in children: I. Study design and study population characteristics. [Endoscopic and conservative treatment of vesicoureteric reflux]. A short-term study of nitrofurantoin prophylaxis in children managed with clean intermittent catheterization. Fosfomycin trometamol versus netilmicin in children's lower urinary tract infections. The length of antimicrobial therapy in upper vs. lower urinary tract infection of childhood. [Prophylaxis of recurrent urinary tract infections in children. Results of an open, controlled and randomized study about the efficacy and tolerance of cefixime compared to nitrofurantoin].
To evaluate the role of primary vesicoureteral reflux (VUR) in increasing the frequency and severity of urinary tract infections (UTIs) and renal parenchymal damage among patients with acute pyelonephritis and to determine whether urinary antibiotic prophylaxis reduces the frequency and/or severity of UTIs and/or prevents renal parenchymal damage among patients with mild/moderate VUR.
                Patients 3 months to 18 years of age with acute pyelonephritis, with or without VUR, were assigned randomly to receive urinary antibiotic prophylaxis or not. Patients were monitored every 3 months for 1 year. Dimercaptosuccinic acid renal scans were repeated at 6 months or if there was a recurrence of febrile UTI. Urinalysis and urine culture were performed at each clinic visit. Renal ultrasound scans and voiding cystourethrograms were repeated at the end of 1 year of follow-up monitoring.
                Of the 236 patients enrolled in the study, 218 completed the 1-year follow-up monitoring. Groups were similar with respect to age, gender, and reflux grade distribution for those with VUR. No statistically significant differences were found among the groups with respect to rate of recurrent UTI, type of recurrence, rate of subsequent pyelonephritis, and development of renal parenchymal scars.
                After 1 year of follow-up monitoring, mild/moderate VUR does not increase the incidence of UTI, pyelonephritis, or renal scarring after acute pyelonephritis. Moreover, a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study. 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.
                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.
                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.
                For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode. There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux.
                One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans.
                The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis.
                Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV. Nephropathy associated with vesicoureteric reflux (VUR) and urinary tract infection can result in end-stage renal failure, hypertension, or both. Whether long-term VUR contributes to these outcomes is unknown. We compared, in a randomised trial, medical with surgical management of children with bilateral severe VUR and bilateral nephropathy.
                We stratified by age and glomerular filtration rate (GFR) 25 boys and 27 girls aged 1-12 years and randomly assigned them to medical or surgical management. At enrolment and 4 years' follow-up we estimated GFR from the plasma clearance of 51Cr-labelled edetic acid (EDTA), and did intravenous urography. We also did a metastable 99mTc-labelled dimercaptosuccinic acid (DMSA) assay and contrast cystography. The change in GFR at 4 years, expressed as a percentage change between enrolment and 4 years, was available for 26 of 27 patients in the medical and 24 of 25 in the surgical group. We assessed GFR in 48 patients 10 years after enrolment.
                Mean GFR at enrolment was 72.4 mL/min per 1.73 m(2) (SD 24.1) in the medical and 71.7 mL/min per 1.73 m(2) (22.6) in the surgical group. The mean percentage change in GFR at 4 years was 2.4% (SE 4.5) versus 4.7% (5.0) in the medical and surgical groups, respectively. The difference in change in GFR at 4 years between the two groups was not significant (7.1%, 95% CI 6.4% to 20.6%).
                Our data do not lend support to the view that the outcome for renal function is improved by surgical correction of VUR in children with bilateral disease. Thirty children with urinary tract infection and nonobstructive vesicoureteral reflux have been followed prospectively for a mean of 17 months. After classification according to age and grade of reflux, 10 patients were assigned at random to treatment with antimicrobial prophylaxis alone or antimicrobial prophylaxis plus corrective surgery. Twenty other patients were also treated with antimicrobial prophylaxis alone. All were assigned at random to treatment with a single daily dose of trimethoprim-sulfamethoxazole or nitrofurantoin. Cultures of urine, complete blood cell counts, and determination of levels of aspartate aminotransferase in serum were performed regularly during follow-up. Both drugs proved effective in prevention of recurrent infection, and no significant hematologic or hepatic abnormalities were noted. Current results suggest that either prophylaxis or surgery may effectively prevent chronic pyelonephritis or reflux nephropathy, but only continuing evaluation of this group of patients will confirm these results. Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux.
                Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test.
                A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042).
                These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux. The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy.
                In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days.
                Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was approximately 8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally.
                Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures. Acute pyelonephritis often leaves children with permanent renal scarring.
                To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days.
                In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars.
                Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups.
                In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring. We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection.
                Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle.
                During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy.
                Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.
                Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. The aim of study is to evaluate the results of endoscopic treatment of vesicoureteric reflux (VUR) comparing with conservative mode.
                In the years 2003-2006 there were forty for children in prospective randomised study enrolled and divided into two groups. Twenty two children 1-40 months old (22.9 months) were operated. Dx/Ha (Deflux) was instilled for VUR grade 3-5. The results of treatment were compared with outcome of twenty two conservatively treated randomly assigned children aged 1-32 months (mean age 13.5 months) Postoperative videourodynamic study was used to evaluate for the presence of VUR and function of the bladder and ultrasound investigation was performed too (exclusion of obstructive megaureter in operated group). There were 22 children controled after instillation. The children were followed 11-24 months. VUR was cured in 12 cases (54.5%) and improved (grade 1-2) in 5 children (66.7%). All children absolved treatment without any complications, excluding one case with obstructive megaureter after pyelonephritis diagnosed. There were 22 children evaluated in conservative group. Five children were cured (22.7%) and VUR was improved (grade 1-2) in four (18.2%)
                Endoscopic miniinvasive instillation of dextranomer is safe and effective treatment of VUR in all age groups with good therapeutical outcome and minimum of adverse effects. Because there is no evidence for the effectiveness of antibiotic prophylaxis in children with neurogenic bladder, the value of once-daily nitrofurantoin macrocrystals was assessed in a selected population with neurogenic bladder due to meningomyelocele. METHODS AND TRIAL POPULATION: Children with significant urinary tract abnormalities other than neurogenic bladder were excluded. A urinary tract "infection" was defined as > or = 10(8) colony forming units of bacteria/L of urine together with pyuria of > or = 50 x 10(6) leukocytes/L, and/or symptoms consistent with an urinary tract infection. Fifty-six children participated in a 24-week double-blinded, placebo-controlled cross-over study. The infection status was assessed at two weekly intervals or if relevant clinical manifestations occurred.
                For the whole trial the average percentage of "infections" per urine sample for each patient was reduced from 39% on placebo to 19% on single daily dose prophylaxis (P < .0003). For the first 12 weeks of the trial corresponding figures were 45% on placebo and 22% on prophylaxis (P < .0018). There was evidence for a marked carryover protective effect of nitrofurantoin into the placebo arm of the trial.
                Nitrofurantoin is an effective prophylactic agent during a 3-month period. Long-term studies are needed to confirm the reasonable expectation of a beneficial effect on urinary tract damage. Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36-48 h after a single oral dose of 1-2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever (less than 38 degrees C), erythrocyte sedimentation rate (less than 25 mm/l h) and C-reactive protein (less than 20 micrograms/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and children. 235 infants and children were randomized to a 10-day and 42-day treatment group and followed-up for 12 months after their first urinary tract infection. The anatomical level of each symptomatic infection was determined using simple laboratory criteria. The two regimens prescribed were equally effective in eradicating the infection, but after the discontinuation of the 10-day treatment with sulfafurazole, 17 (23%) of 73 patients with their upper urinary tract infection experienced a recurrence within one month, as compared to only one (1) of 76 subjects in the 42-day therapy group. After the phase of early recurrence, there was no difference in recurrence rate between these groups. The early recurrences were associated with the patient's early age and a short duration of symptoms before therapy. The recurrence rate of first lower UTI after 10-day therapy was significantly lower than that after 42-day treatment. The duration of antimicrobial therapy for childhood urinary tract infection should be adjusted according to the patient's age and the anatomical level of the infection. 10-day treatment may not be sufficient to prevent early recurrence of pyelonephritic infections in infants under 6 months of age. Urinary tract infections are quite frequent in children. Urinary tract obstruction combined with recurrent urinary tract infections increase the risk for renal impairment. Therefore prophylaxis of reinfection is an important nephroprotective procedure. The aim of this open, controlled, randomised pilot study was to compare the efficacy and tolerance of a low dose prophylaxis with Cefixime versus Nitrofurantoin. 60 girls aged 1 to 11 years with at least 2 urinary tract infections within the preceding year were included in the study. The minimum duration of therapy was 6 months and was extended to 12 months for most of the children. The number of recurrent infections was the main criteria for efficacy evaluation, whereas adverse events were analysed to evaluate tolerance. Statistical significant differences between the two treatment groups, regarding recurrence rates could not be demonstrated. Tolerance was comparable in both groups. The influence on gut flora of cefixime given as a low dose regimen over a long period of time corresponds with already published results and was not correlated with a higher number of gastrointestinal side effects.
                Low-dose Cefixime (2 mg/kg bodyweight) is effective and well tolerated in the prophylaxis of recurrent urinary tract infections. Efficacy and tolerance of cefixime were comparable to the results obtained with nitrofurantoin. Due to the small number of patients this study was only a pilot study. Low-dose cefixime, however, could become an alternative to standard regimens in the prophylaxis of recurrent urinary tract infections. This should be investigated in further studies.
Compared with no treatment, use of long-term, low-dose antibiotics did not significantly reduce the number of repeat symptomatic and febrile UTIs in children with VUR. Considerable heterogeneity in the analyses and inclusion of only one adequately blinded study, made drawing firm conclusions challenging. Antibiotic prophylaxis significantly reduced the risk of developing new or progressive renal damage, but assuming an 8% baseline risk, 33 children would need long-term antibiotic prophylaxis to prevent one more child developing kidney damage over the course of two to three years.
The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear. Eight children would require combined surgical and antibiotic treatment to prevent one additional child developing febrile UTI by five years, but it would not cause fewer children developing renal damage.