PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1064-1071 (doi:10.1542/peds.2007-3770)
ARTICLE |
Prophylaxis After First Febrile Urinary Tract Infection in Children? A Multicenter, Randomized, Controlled, Noninferiority Trial
Departments of a Pediatric Nephrology
b Nuclear Medicine
c Pediatrics
e Epidemiology Unit
p Pediatric Emergency Department, Azienda Ospedaliera-University of Padua, Italy; Pediatric Unit
d Oderzo
f Castelfranco Veneto
g Bologna
h Mestre-Venezia
i Soave
j Bolzano
k Ravenna
l Piove di Sacco-Chioggia
m Verona-Borgo Trento
n Bentivoglio
q Thiene, Italy
o General Practitioner, San Donà di Piave-Venezia, Italy
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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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.
Key Words: urinary tract infection • antibiotic prophylaxis • renal scar • DMSA scan
Abbreviations: UTI—urinary tract infection • RR—relative risk • CI—confidence interval • VUR—vesicoureteral reflux • ITT—intention-to-treat • DMSA—dimercaptosuccinic acid • VCUG—voiding cystourethrography • IQR—interquartile range
Febrile urinary tract infections (UTIs) are considered the most common serious bacterial infections that occur in infancy and early childhood in the developed world.1 Fifteen percent of cases are associated with renal scarring,2 which is responsible for the long-term medical consequences (proteinuria, hypertension, chronic kidney damage).3–5 The frequency of reinfection during the first year after a UTI has been estimated to be up to 30%.6–8 Antibiotic prophylaxis has been widely used despite the evidence supporting its efficacy is weak.
In 3 studies (n = 153) from the 1970s, long-term (10 weeks to 12 months) antibiotics reduced the risk for repeat positive urine cultures (relative risk [RR]: 0.4 [95% confidence interval (CI): 0.26–0.62]) compared with placebo or no prophylaxis.9–11 Only 1 study reported an increased risk (RR: 1.93 [95% CI: 0.63–5.92]) of recurrence of symptomatic UTI in 27 children who received prophylaxis versus 32 children who received placebo.9 In these 3 trials, the study population (mainly girls and few patients with urinary tract abnormalities) was small and did not reflect the pediatric population to whom prophylaxis is usually given. Bacterial resistance was not considered.
In 1 randomized study,12 the role of prophylaxis in reducing the frequency of UTIs among patients with acute pyelonephritis was not supported. This trial showed that the use of antibiotic prophylaxis was not only ineffective but also harmful: among children with vesicoureteral reflux (VUR), recurrent acute UTIs was observed for 7 of 55 patients who received urinary antibiotic prophylaxis, compared with only 1 of the 58 patients with no prophylaxis (P = .0291). In all of the 7 cases, the offending bacteria showed resistance to the antibiotic used for prophylaxis. In this study, the antimicrobial treatment of the acute episode was not standardized, intention-to-treat (ITT) analysis was not performed, and the age range was extremely wide. We conducted a noninferiority, randomized, controlled trial to determine whether no prophylaxis for children who were aged 2 months to 7 years and had a first febrile UTI, with or without the presence of primary nonsevere VUR, is similar to antimicrobial prophylaxis for 12 months in producing the recurrence of febrile UTIs.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The study is a controlled, randomized, multicenter, open-labeled, parallel-group trial. It was originally designed as a 3-arm trial subsequently amended to be a 2-arm noninferiority study. It was conducted from May 2000 to August 2006 at 22 pediatric units located in Northeast Italy, coordinated by the Unit of Nephrology, Dialysis and Transplantation of the Pediatric Department of Padova. The ethics committee of each participating center approved the protocol. The parents of each child signed an informed consent before participation.
Patient Inclusion and Exclusion Criteria
The study population was recruited among children who had a first episode of febrile UTI, with or without primary nonsevere VUR (first to third degree). Recruitment was confined to children who were aged 2 months to 7 years and had normal renal function.13 Exclusion criteria were complex urologic malformations and/or severe renal damage (dimercaptosuccinic acid [DMSA] scintigraphy showing a relative function of 1 kidney <30%).
The diagnosis of first febrile UTI at presentation was made by fever 
38°C, pyuria (2 concordant consecutive test results with white cell counts 25/µL), and urine culture (2 concordant consecutive tests with growth of only 1 microorganism 100000 colony-forming units/mL). Urine was collected with a sterile urinary bag; the 2 concordant consecutive urinalysis and culture were required to minimize the risk for false-positive tests. Children also had to have at least 2 of fever 38°C, raised inflammatory indices in the first 48 hours (erythrocyte sedimentation rate 30 mm in the first hour or C-reactive protein 3 times upper limit of normal values, or both), and neutrophil count above the normal values for age.
Imaging Studies
Prerandomization
Ultrasonography and DMSA renal scans were performed within 10 days from commencement of antibiotic for the febrile UTI. Focal or diffuse areas of decreased uptake in the first DMSA scan, without evidence of cortical loss, were considered indicative of acute pyelonephritis. Voiding cystourethrography (VCUG; radiology, with 1 filling) was performed within 2 months of UTI.
Postrandomization
Repeat DMSA scans were planned 12 months from randomization, or, when a new episode of febrile UTI occurred, at least 6 months after infection. Renal scarring was defined as decreased uptake with distortion of the contours or as cortical thinning with loss of parenchymal volume. Two nuclear physicians, who were blinded to the patients' test results, interpreted the scans independently. Discrepancies were resolved by discussion between the assessors.
Antibiotic Treatment of Febrile UTI
Antibiotic treatment of the initial UTI was either intravenous ceftriaxone for 3 days followed by oral co-amoxiclav for 7 days or oral treatment only with co-amoxiclav for 10 days. After completion of treatment, all children were given prophylaxis until the VCUG was performed.
Randomization
The randomization scheme was computer-generated by the coordinating center. Randomization, 1:1:1 for the 3 arms, was stratified by center, gender, and clinical group on the basis of presence or absence of VUR and of the parenchymal localization of the acute UTI. There were 3 groups: (1) acute positive DMSA without VUR, (2) acute negative DMSA with VUR, and (3) acute positive DMSA with VUR. Each participating center received 6 series with allocation codes. The series were 1 for each stratum, and each series contained 12 sealed, opaque envelopes. Every envelope was numbered with a sequential number. Each participating center assigned every enrolled child to a stratum (on the basis of gender and clinical group). The allocation code for that child was then assigned, opening the next envelope in that stratum series.
In the second part of the study, the 1:1 randomization scheme was automatically generated, stratified as before, and kept centrally. After assigning the child to a stratum, the centers received the allocation treatment from the coordinating center. Investigator meetings to standardize good clinical practice were organized before and during the study.
Study Interventions
Recruited patients were allocated to group A, no prophylaxis, or group B, prophylaxis (co-trimoxazole or co-amoxiclav both at the dosage of 15 mg/kg per day). Outpatient urine cultures were performed monthly for the first 6 months and then every 2 months; outpatient clinic visits were at 6 and 12 months. A DMSA scheduled at 12 months ended follow-up for all patients. Children who experienced 2 recurrent febrile UTIs were switched to prophylaxis when allocated to no prophylaxis and to other antibiotic or referred for VUR surgery when already allocated to prophylaxis. Data collected were symptoms and signs of UTI (urinalysis, urine culture), compliance to treatment and adverse effects, and resistance to the prophylactic antibiotic in case of positive urine cultures. Compliance was evaluated by assessment of antimicrobial activity in urine at the routine urine cultures and by a questionnaire with a visual analogic scale of parents' assessment of "difficulty" in following treatment.
Outcome Measurements
The primary end point was the first recurrence of febrile UTIs in the 12 months after randomization. Recurrent UTI was defined by presence of fever (>38°C), pyuria, and urine culture as defined in the inclusion criteria. Additional recurrences and arm switches were therefore not accounted as "failure" per se.
Secondary end point was the rate of new renal scarring defined as scarring, other than at the site of the initial pyelonephritis, after 12 months. Exploratory analyses were also performed to evaluate the risk for repeat positive urine cultures and the rate of scarring at the site of the initial infection as potential end points.
Study Design and Sample Size
The study was designed as a controlled, randomized, open-label, 3-armed, parallel-group study, comparing no prophylaxis, prophylaxis with co-trimoxazole, and prophylaxis with co-amoxiclav. A first comparison was planned between no prophylaxis and prophylaxis, with a subsequent comparison between the 2 antibiotics if the pooling of prophylaxis had shown a better outcome.
The study aimed to enroll 660 patients in a 1:1:1 ratio across the 3 groups. Enrollment was slower than anticipated, reaching 237 patients by August 2003 (evenly allocated to no prophylaxis, co-trimoxazole, and co-amoxiclav). Thus, following the recommendation of the Data and Safety Monitoring Committee to take action to be able to complete enrollment in a reasonable time frame, we decided to modify the study design, maintaining the primary objective (comparison between prophylaxis and no prophylaxis) and abandoning the comparison between the 2 antibiotics regimens.
The new sample size for the 2-arm, noninferiority trial was calculated to be 313 patients (rounded to 340, for possible dropouts), setting power at 70% and 
error of .05 (1-sided), maintaining the assumption of 20% incidence of recurrence, and considering an upper confidence limit of 30% for noninferiority for the no-prophylaxis arm. The patients who were enrolled after the amendment were randomly assigned in a 1:1 ratio between no prophylaxis and prophylaxis, with a final expected ratio of 1:1.5.
Statistical Analysis
In the ITT analysis, 2 scenarios were considered for patients who exited the trial (lost to follow-up): (1) all "failures" and (2) all "successes." The efficacy comparison between "prophylaxis" and "no prophylaxis" was performed considering the differences between treatments and the 95% CI for this difference. The binomial outcome measures were tested using the 
2 test (Fisher test and Pearson test); the numerical outcome measures were tested using Student's t test or the Mann-Whitney test, as appropriate. A multivariate survival analysis was conducted using the Cox proportional hazards model. The survival analyses conducted using the Cox proportional hazards model have been integrated with the evaluation of Kaplan-Meier curves, log-rank tests. and/or Wilcoxon's test to detect significant differences in the curves. The number of patients to be treated was calculated as previously suggested.14
The software Stata 9.0 (Stata Corp, College Station, TX) was used for the statistical analysis. A secondary analysis comparing the effectiveness of the prophylactic treatment in subgroups of patients defined by age, gender, and grade of reflux was performed.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Between July 2000 and September 2005, 22 centers enrolled and randomly assigned 338 patients: 127 (37.6%) to no prophylaxis and 211 (62.4%) to prophylaxis (113 [54%] co-amoxiclav and 98 [46%] co-trimoxazole). The final randomization ratio was 1:1.7 (expected 1:1.5). Follow-up was completed in August 2006. Three patients were wrongly enrolled (2 did not complete the screening work out; 1 older than 7 years). Adherence to the protocol was good: 26 patients who were lost to follow-up were evenly distributed in the 2 arms (10 [7.9%] of 127 and 16 [7.6%] of 211). Patient allocation and compliance to protocol are shown in Fig 1.
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The acute infection was treated with initial intravenous antibiotics for 151 (45%) patients and with complete oral treatment for 183 (55%), unknown in 4. The distribution of oral and intravenous treatment was similar in the 2 arms (P = .22). All children were given a prophylactic regimen of co-amoxiclav until VCUG was performed for a median (interquartile range [IQR]) period of 40 days (33–50); no prophylaxis: 40 (32–51); prophylaxis: 41 (34–50). Baseline characteristics were similar for children who were randomly assigned in the 2 arms (Table 1).
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Primary Outcome
Febrile UTIs were not significantly different between the 2 groups during follow-up: 12 (9.45%) of 127 in the no-prophylaxis group and 15 (7.11%) of 211 (risk difference: 2.34% [95% CI: 3.8%–8.4%]; Table 2) . These results hold true even once patients are stratified by grade of VUR (Table 2). These data were obtained with ITT analysis, considering the patients lost to follow-up before the 12-month visit as having no recurrence. Data are shown also as a Kaplan-Meier for time free of events in Fig 2. Median time (IQR) to febrile recurrences was 113 days (57–192) with no significant difference between the 2 groups (log-rank test P = .36). We found similar results when we counted all patients who were lost to follow-up as having a recurrence during the 12 months and with an on-treatment analysis (Table 2). The exploratory analysis showed that the rate of repeat positive urine culture and concomitant positive urinalysis was significantly different between the 2 groups: 24 (18.9%) of 127 on no prophylaxis and 20 (9.5%) of 211 on prophylaxis (P = .02).
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Age, gender, VUR grade, treatment of the initial UTI (oral versus intravenous), and prophylaxis were considered in bivariate analysis: younger age and VUR grade were associated with recurrence of febrile UTI. The mean age was 7.1 vs 14.6 months for children with recurrence versus no recurrence (P = .02). The rate of recurrences increased with the grade of VUR, from 8 (3.8%) of 210 for patients with no VUR to 2 (6.7%) of 30, 5 (8.6%) of 58, and 12 (30%) of 40 for patients with VUR grades I, II, and III, respectively (P < .01). In the Cox proportional hazards model, no prophylaxis was not a risk factor for recurrence of febrile UTIs; older age was confirmed to be protective and grade III reflux to be a risk factor (Table 3). The number of patients to be treated to prevent a febrile recurrence was 41.7 children for 1 year.
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Secondary Outcomes
A total of 87% (295) of enrolled patients had the DMSA scan at 1 year with a median (IQR) time to DMSA of 351 days (329–385) after enrollment. A new renal scar (in a different site from the initial pyelonephritis) was found in 4 (1.4%) of 295 patients (Table 2); the new scars occurred in 1 kidney without reflux, 1 kidney with grade II reflux, and 2 kidneys with grade III reflux. No difference was found in no prophylaxis (2 [1.9%] of 108) versus prophylaxis (2 [1.1%] of 187; risk difference: 0.8% [95% CI: –2.1%–3.7%]). Similar results were found in exploratory analysis, comparing the rate of scars at the site of the first pyelonephritis: 31 (28.7%) of 108 vs 48 (25.7%) of 187 (Table 2) and when considering the rate of new scars in the children with recurrences (2 [17%] of 12) for no prophylaxis and for prophylaxis (2 [13%] of 15).
Urine Cultures
A total of 2422 routine urine cultures and urinalyses were performed. The cause of the 27 recurrences were similar in the 2 groups and were attributed to Escherichia coli in 19 (70%) of 27, Proteus mirabilis in 2 of 27 (7%), Enterobacter in 2 of 27 (7%); Pseudomonas aeruginosa, Klebsiella oxytoca, Klebsiella pneumoniae, and Citrobacter in 1 (4%) of 27 each. All but 1 of the 9 recurrences that were attributed to resistant bacteria were in the prophylaxis group, and the 1 that occurred in the no-prophylaxis group was in a child who had been switched to prophylaxis. The isolated resistant bacteria were E coli in 6 cases and P mirabilis, Enterobacter, and K pneumoniae in 1 case each.
Other Antibiotics Used
Forty-five of 338 patients changed allocated arm or antibiotic: 9 allocated to no prophylaxis switched to prophylaxis (7 because of UTI recurrence, 2 for unknown reasons); 15 switched from co-amoxiclav to other antibiotics and 3 stopped; 12 switched from co-trimoxazole to other antibiotics and 6 stopped. One patient underwent surgery for VUR.
Adherence
A total of 340 of 851 urine cultures were tested for antimicrobial activity in the no-prophylaxis and 578 of 1571 in the prophylaxis arm: 10 (2.9%) and 411 (71.1%), respectively, tested positive. The reported compliance (visual analog scale questionnaire) was good for 86% of patients.
Adverse Events
Twenty-five (7.3%) children experienced minor adverse effects during the 12 months of follow-up. All patients were on prophylaxis: 15 on co-amoxiclav and 10 on co-trimoxazole. Adverse events were mainly vomiting or gastrointestinal intolerance.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Children with febrile UTIs and/or VUR are usually given prophylactic antibiotics despite there being no evidence that this approach is protective against renal scarring or long-term medical complications.6,15 Furthermore, bacterial resistance to antibiotics is becoming a major issue worldwide, antibiotic use being increasingly recognized as the main force producing this resistance.16,17 One study showed that children were the main antibiotic consumers, with usage rates 3 times higher than that of older patients, thereby increasing their exposure to the risk for bacterial resistance.18 In accordance, in our study, the higher risk for resistance was in the prophylaxis arm; therefore, the potential benefit of antibiotics has to be weighted with the high risk for selecting resistant bacteria.
According to our definition of noninferiority, this study showed that during a period of 12 months, no prophylaxis had no greater risk for recurrent febrile UTIs than prophylaxis. At the study completion, 338 children were enrolled, giving a final randomization ratio of 1:1.7 and providing 72% posthoc power compared with 70% as intended. The number of children who were lost to follow-up was small (7.7% at the 12-month follow-up) and evenly distributed between the 2 arms of the study. This fact, together with the low number of recurrent febrile UTIs, makes it unlikely that the missing data could influence the risk difference of the recurrence rate. A weakness of our study is that it was not double-blinded and placebo-controlled. We believe that the actual design of our study does not permit major bias, because the study has objective end points: the diagnosis of recurrent UTI has precise criteria, patients and their doctors were appropriately instructed to suspect recurrent infections, and the presence of scar was evaluated blindly by 2 nuclear physicians.
The results of our study are in accordance with the study by Garin et al12 in showing no benefit of prophylaxis on no prophylaxis and in revealing higher prevalence of resistances in the prophylaxis arm. Anyhow, in our study children with grade III reflux and no prophylaxis experienced an increased number of recurrent infections, although not statistically significant, whereas in the study by Garin et al,12 treatment was not just ineffective but even harmful. Additional specifically designed investigations, with a much larger population with reflux, are needed.
There were a significantly higher number of repeat positive urine cultures in the arm with no prophylaxis (mean difference: 9.4 [95% CI: 1.5–17.3]), and this has been the driving force behind the use of prophylactic antibiotics; however, we believe that repeat positive urine cultures in absence of fever or other symptoms of parenchymal localization of the infection are not clinically relevant and do not produce renal scars. This is confirmed by the fact that the number of new scars is low: 1.4%. It is worth noting that this is the first study to differentiate between scars as a result of repeat infections and those as a result of original pyelonephritis. The latter were much more frequent (79 [27%] of 295). These result from the first UTI are unrelated to prophylaxis and did not differ between the 2 study groups. Although the risk for repeat febrile UTIs is 8.3% per year for our population, concordant with a recent cohort study19 that showed a 12% recurrence per year, the risk for renal damage from repeat infections is very low and, per se, does not justify the need for prophylaxis in our population.
Prophylaxis was associated with a higher number of febrile UTIs as a result of bacteria resistance. Co-trimoxazole and co-amoxiclav are 2 old and frequently used antibiotics in our area. New antibiotics, with a better resistance profile, could have allowed a lower number of recurrences in the prophylaxis arm.
It is worth remembering that, per protocol, all children were maintained on prophylaxis until cystography (median: 40 days) from the acute infection; therefore, we do not have data on a complete prophylaxis-free protocol, and we cannot comment on the role of antibiotic prophylaxis in preventing infections during this early post-UTI period. The study shows that prophylaxis, conducted for 
1 month for all children, can be safely stopped afterward. The recently published study by Garin et al12 seems not to have such treatment phase. Anyhow, there is no comment in the article of repeated UTIs during this prophylaxis-free period and whether any patient was excluded by the trial because of infections before the VCUG. To have additional recommendations on the role of a complete prophylaxis-free regimen, we need another study to compare stopping of antibiotic immediately after treatment completion.
From the multivariate analysis, grade III reflux represents the only risk factor for the recurrence of febrile UTIs. No prophylaxis is not a risk factor. As expected, increasing age protects from recurrences (Table 3). It is interesting that a recent study19 showed, in multivariable Cox time-to-event models, that factors that were associated with increased risk for recurrent UTI included age 3 to 5 years and higher grades (IV–V) of VUR. Prophylaxis was not associated with decreased risk for recurrent UTI but was a risk factor for antimicrobial resistance.
Our study population consisted of children of both genders, aged <7 years, mostly (309 of 336) with a documented parenchymal renal localization of the infection. A total of 128 (38%) of 336 had primary VUR grades I to III. Exclusion criteria were urinary tract disorders as a result of complex urologic malformations, DMSA scan showing a relative function of 1 kidney <30%, and VUR grades IV and V. These criteria are routinely evaluated in clinical practice when considering prophylaxis, meaning that the results of this study are readily applicable.
We excluded children with grades IV to V reflux and/or monolateral or bilateral renal hypodysplasia, because we considered those children particularly at risk for repeat infections and renal damage. Our conclusions do not apply to children with higher degrees of reflux. This however opens the debate as to the need for routine VCUG in the first place for children with normal renal ultrasound and a first febrile UTI, who have a very low probability to have a high-degree reflux.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our study shows that prophylaxis does not reduce the rate of febrile UTI recurrence during 12 months after the first episode of febrile UTI in children with or without the presence of primary nonsevere reflux. Patients with grade III VUR seem to have significantly different results from those with lower grades or no reflux.
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ACKNOWLEDGMENTS |
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This study was supported by Region of Veneto (research project 40/01) and association Il Sogno di Stefano (Stephen's Dream).
We thank all the members of Italian Renal Infection Study Group in children (IRIS), who made the performance of this study possible. We particularly thank Daniela Gobber (epidemiologist), who died 2 years ago. We also thank, Andrea Ponzoni for statistical analysis and Manola Bettio and Pia-Sophia Wool for reviewing the manuscript.
Data and Safety Monitoring Committee: Roberto Buzzetti (epidemiologist), Modena; Giovanni Capasso (pediatric nephrologist), Naples; and Roberto D'Amico (statistician), Modena. Participants of the IRIS2 study: I. Marella, A. Budini (Adria); L. Marcazzò, S. Bellato (Arzignano); G. Audino, G. Picco (Bassano); P. Colleselli, D. Scorrano (Belluno); L. Pavanello (Castelfranco); C. Crivellaro (Chioggia); G. Cattarozzi, M. Pitter, A. Ballan (Dolo/Mirano); F. Rossetti, V. Cannella (Este/Monselice); G. Svaluto-Moreolo, Caddia (Feltre); G. Pozzan, F. Maschio (Mestre); P. Brisotto, N. Crema, S. Breseghella (Montebelluna); P. Luxardo, A. Toffolo (Oderzo); G. Zacchello, G. Montini, L. Murer, C. Carasi, B. Andreetta, S. Comacchio, L. Rigon, S. Sartori, L. Tomasi, R. Pertile, D. Gobber (epidemiologist), A. Ponzoni (statistician) (Padua); A. Truini (Piove di Sacco); P.G. Flora, M. Ranieri (San Donà); R. Dall'Amico, L. Donello (Thiene); G. Marcer, S. Zanchetta (Soave); M. Del Majno, M. Gheno (Venice); P. Biban, P. Fortunati (Verona-Borgo Trento); M.G. Santangelo, O. Gianesini (Vicenza); A. Corsini (Bentivoglio); P.P. Molinari (Bologna); A. Zucchini (Faenza/Lugo); Venturolli (Forlì); L. Serra (Imola); L. Casadio (Ravenna); M. Principi (Macerata); M. Pitschiller, W. Cassar (Bolzano); M. De Marini, G. Crescenzi (Cuneo).
Dr Montini had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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FOOTNOTES |
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Accepted Mar 3, 2008.
Address correspondence to Giovanni Montini, MD, Nephrology, Dialysis and Transplant Unit, Pediatric Department, Azienda Ospedaliera-University of Padova, Via Giustiniani, 3, 35128 Padova, Italy. E-mail: montini{at}pediatria.unipd.it
The authors have indicated they have no financial relationships relevant to this article to disclose.
This trial has been registered at www.clinicaltrials.gov (identifier NCT00156546).
| What's Known on This Subject Antibiotic prophylaxis has been widely used after a febrile urinary tract infection, despite the evidence supporting that its efficacy is weak.
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| What This Study Adds Antibiotic prophylaxis, commonly used to reduce the risk for repeat febrile urinary tract infections, does not reduce the rate of recurrence during 12 months after the first episode in children with or without the presence of primary nonsevere reflux.
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[Abstract/Free Full Text] - Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials.
JAMA. 2007;298
(2):179
–186
[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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