Antibiotics for the prevention of urinary tract infection in children: A systematic review of randomized controlled trials

doi:10.1067/mpd.2001.113785

The Journal of Pediatrics

Volume 138, Issue 6, June 2001, Pages 868-874

https://doi.org/10.1067/mpd.2001.113785 Get rights and content

Abstract

Objective: The objective was to evaluate the effectiveness of low-dose, long-term antibiotics for the prevention of symptomatic urinary tract infection (UTI) in children. Design: This was a systematic review of randomized controlled trials with a random effects model meta-analysis. Participants: Five trials involving 463 children were performed. Results: Three trials (n = 392) evaluated the effectiveness of long treatment courses of antibiotics (2 to 6 months) for children with acute UTI to prevent subsequent, off-treatment infection. Only 2 trials (n = 71) evaluated the effectiveness of long-term, low-dose antibiotics to prevent on-treatment UTI. Very few of the children enrolled in the trials were boys, had abnormal renal tracts, or were infants. The trial quality was poor, with a lack of blinding, and unstated UTI definitions were almost universal. Long-term antibiotic administration reduced the risk of UTI with treatment (relative risk 0.31, 95% confidence limits 0.10 to 1.00), but there was significant heterogeneity (Q = 13.45, P <.01), and there was no sustained benefit once antibiotics had ceased (relative risk 0.79, 0.61 to 1.02). Conclusions: Methodologic and applicability problems with published trials mean that there is considerable uncertainty about whether long-term, low-dose antibiotic administration prevents UTI in children. Well-designed, randomized, placebo-controlled trials are still required to evaluate this commonly used intervention.(J Pediatr 2001;138:868-74)

Section snippets

Inclusion Criteria

All randomized controlled trials and quasi-randomized (allocation based on alternation, date of birth, hospital medical record number) controlled trials that compared antibiotic treatment with placebo or no treatment for the prevention of recurrent UTI were included. This systematic review was not designed to evaluate the short-term efficacy of antibiotics given over the short term for UTI to eradicate pathogenic organisms. Instead, we assessed the efficacy of antibiotics given over the long

Literature Search

Of >900 titles read, 595 abstracts were analyzed, and 581 were excluded because they were clearly not clinical trials or did not concern antibiotics for the prevention of recurrent UTI in children. Full assessment of the remaining 14 papers was performed, and 5 relevant randomized controlled trials were identified.

Trial Characteristics

Five trials (n = 463 children) examined the recurrence risk for UTI while children were receiving antibiotics (Table I).14, 15, 16, 17, 18

. Characteristics of trials using long-term

Discussion

Randomized controlled trial evidence to support the widespread use of antibiotics to prevent recurrent UTI in children is weak. With approximately 2% to 8% of children having a UTI and one third of these children also having vesicoureteric reflux, approximately 1% of the entire childhood population has reflux, is at risk of recurrent UTI, and therefore may be given long-term, low-dose antibiotics.2, 4 This study shows that this very commonly used intervention is based on only 5 controlled

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Cited by (96)

Asian guidelines for urinary tract infection in children
2021, Journal of Infection and Chemotherapy
Citation Excerpt :
Due to the facts that both substances in many countries are restricted on admission in early infancy, oral cephalosporines are preferred in this age group. The efficacy of antimicrobial prophylaxis per se has been questioned in several reviews [74–78] which concluded that there was no clear association between recurrent UTI and VUR, and renal damage, renal scarring, hypertension, and end-stage renal disease. Two prospective multicenter RCT study randomized children (n = 100, and n = 225) with febrile UTI and VUR to receive either trimethoprim/sulfamethoxazole or no treatment [79,80].
The followings are the level of evidence (LE) and grade of recommendation (GR) on pediatric UTI in Asia. Classification according to the sites of infection (lower versus upper tract), the number of episode (first versus recurrent), the severity (simple versus severe), or the existence of complicating factor (uncomplicated versus complicated) is useful to differentiate children with UTI whether they are at risk of renal damage or not (LE: 2, GR: B). Diagnosis of UTI requires both urinalysis that suggests infection and positive urine culture (LE:3, GR B). For pre-toilet trained children, urine specimen for culture should be collected by urethral catheterization or suprapubic aspiration. For toilet trained children, midstream clean catch urine is reliable (LE: 3, GR: A). Urine culture is considered positive if it demonstrates growth of a single bacterium with the following colony counts: (1) any growth by suprapubic aspiration, (2) >5 × 104 CFU/ml by urethral catheterization, or (3) >100,000 CFU/ml by midstream clean catch (LE:3, GR: B). For children with febrile UTI, renal and bladder ultrasonography (RBUS) should be routinely performed as soon as possible (LE: 3, GR: C). RBUS should be followed up 6 months later in children with acute pyelonephritis and/or VUR (LE: 3, GR: C). Acute DMSA scan can be performed when severe acute pyelonephritis or congenital hypodysplasia is noted on RBUS or when the diagnosis of UTI is in doubt by the clinical presentation (LE: 3, GR: C). Late DMSA scan (>6 months after the febrile UTI) can be performed in children with severe acute pyelonephritis, high-grade VUR, recurrent febrile UTIs, or abnormal renal parenchyma on the follow-up RBUS (LE: 3, GR: C). Top-down or bottom-up approach for febrile UTI is suggested for the diagnosis of VUR. For top-down approach, VCUG should not be performed routinely for children after the first febrile UTI. VCUG is indicated when abnormalities are apparent on either RBUS or DMSA scan or both (LE: 2, GR: B). VCUG is also suggested after a repeat febrile UTI (LE:2, GR: B).
Appropriate antibiotic should be given immediately after urine specimen for culture has been obtained (LE:2, GR: A). Initiating therapy with oral or parenteral antibiotics is equally efficacious for children (>3 months) with uncomplicated UTI (LE: 2: GR: A). The choice of empirical antibiotic agents is guided by the expected pathogen and the local resistance patterns (LE: 2, GR: A). For children with febrile UTI, the total course of antibiotic therapy should be 7–14 days (LE: 2, GR: B). Circumcision may, but not definitively, reduce the risk of febrile UTI in males and breakthrough febrile UTI in males with VUR. Circumcision should be offered to uncircumcised boys with febrile UTI and VUR in countries where circumcision is accepted by the general population (LE: 3, GR: B), while in countries where childhood circumcision is rarely performed, other measures for febrile UTI/VUR should be the preferred choice (LE: 4, GR: C). Bladder bowel dysfunction (BBD) is one of the key factors of progression of renal scarring (LE: 2). Early recognition and management of BBD are important in prevention of UTI recurrence (LE:2, GR: A). Antibiotic prophylaxis to prevent recurrent febrile UTI is indicated in children with moderate to high grade (III–V) VUR (LE: 1b, GR: A). Surgical intervention may be used to treat VUR in the setting of recurrent febrile UTI because it has been shown to decrease the incidence of recurrent pyelonephritis (LE: 2, GR: B).
Follow-up after infants younger than 2 months of age with urinary tract infection in Southern Israel: Epidemiologic, microbiologic and disease recurrence characteristics
2016, Brazilian Journal of Infectious Diseases
The timing of most recurrences after neonatal urinary tract infection is during the first year of life, with peak incidence 2–6 months after the initial infection. Information on the microbiologic characteristics of recurrent urinary tract infection episodes in relation to the microbiology of the initial episodes is limited.
To analyze the epidemiologic/microbiological characteristics of 1st and recurrent urinary tract infection in infants <2 months of age.
A retrospective study including all infants <2 months of age with urinary tract infection admitted during 2005–2009 and followed till the age of 1 year.
151 neonates were enrolled (2.7% of all 5617 febrile infants <2 months of age admitted). The overall incidence of urinary tract infection occurring during the first 2 months of life was 151/73,480 (0.2%) live births during 2005–2009 in southern Israel (2.1 cases/1000 live births). One pathogen was isolated in 133 (88.1%); Escherichia coli, Klebsiella spp., Enterococcus spp., Morganella morganii, Proteus spp., and Enterobacter spp. represented the most common pathogens (57.9%, 12.2%, 7.9%, 6.7%, 6.1%, and 5%, respectively). Trimethoprim/sulfamethoxazole, ampicillin, and cefuroxime-axetil were the most commonly recommended prophylactic antibiotics (45%, 13.2%, and 8%, respectively). Twenty-three recurrent urinary tract infection episodes were recorded in 20 (13.2%) patients; 6/23 (26%) were diagnosed within one month following 1st episode. E. coli was the most frequent recurrent urinary tract infection pathogen (12/23, 52.2%). No differences were recorded in E. coli distribution between first urinary tract infection vs. recurrent urinary tract infection. Seventeen (74%) recurrent urinary tract infection episodes were caused by pathogens different (phenotypically) from those isolated in 1st episode. Recurrent urinary tract infection occurred in 25.0%, 8.3%, and 0 patients recommended trimethoprim/sulfamethoxazole, cefuroxime-axetil, or amoxicillin prophylaxis, respectively.
(1) The study determined the incidence of urinary tract infection in febrile infants <2 months of age in Southern Israel; (2) E. coli was responsible for the majority of first and recurrent urinary tract infection; (3) recurrent urinary tract infection was caused mostly by pathogens different than the pathogens isolated at initial episode.
Economic analysis of continuous antibiotic prophylaxis for prevention of urinary tract infections in infants with high-grade hydronephrosis
2015, Journal of Pediatric Urology
Citation Excerpt :
A further assumption was that the risk of surgical intervention did not differ between treatment groups, and that no patients from either group required surgery during the first 2 years of life. Current literature on rates of surgery in the high-grade HN population reflected no differences based on CAP status [3]. Finally, the last assumption was that the probability of developing a UTI in year 2 was independent of the patient's UTI status in year 1.
For infants with hydronephrosis, continuous antibiotic prophylaxis (CAP) may reduce urinary tract infections (UTIs); however, its value remains controversial. Recent studies have suggested that neonates with severe obstructive hydronephrosis are at an increased risk of UTIs, and support the use of CAP. Other studies have demonstrated the negligible risk for UTIs in the setting of suspected ureteropelvic junction obstruction and have highlighted the limited role of CAP in hydronephrosis. Furthermore, economic studies in this patient population have been sparse.
This study aimed to evaluate whether the use of CAP is an efficient expenditure for preventing UTIs in children with high-grade hydronephrosis within the first 2 years of life.
A decision model was used to estimate expected costs, clinical outcomes and quality-adjusted life years (QALYs) of CAP versus no CAP (Fig. 1). Cost data were collected from provincial databases and converted to 2013 Canadian dollars (CAD). Estimates of risks and health utility values were extracted from published literature. The analysis was performed over a time horizon of 2 years. One-way and probabilistic sensitivity analyses were carried out to assess uncertainty and robustness.
Overall, CAP use was less costly and provided a minimal increase in health utility when compared to no CAP (Table). The mean cost over two years for CAP and no CAP was CAD$1571.19 and CAD$1956.44, respectively. The use of CAP reduced outpatient-managed UTIs by 0.21 infections and UTIs requiring hospitalization by 0.04 infections over 2 years. Cost-utility analysis revealed an increase of 0.0001 QALYs/year when using CAP. The CAP arm exhibited strong dominance over no CAP in all sensitivity analyses and across all willingness-to-pay thresholds.
The use of CAP exhibited strong dominance in the economic evaluation, despite a small gain of 0.0001 QALYs/year. Whether this slight gain is clinically significant remains to be determined. However, small QALY gains have been reported in other pediatric economic evaluations. Strengths of this study included the use of data from a recent systematic review and meta-analysis, in addition to a comprehensive probabilistic sensitivity analysis. Limitations of this study included the use of estimates for UTI probabilities in the second year of life and health utility values, given that they were lacking in the literature. Spontaneous resolution of hydronephrosis and surgical management were also not implemented in this model.
To prevent UTIs within the first 2 years of life in infants with high-grade hydronephrosis, this probabilistic model has shown that CAP use is a prudent expenditure of healthcare resources when compared to no CAP.
Pilot randomized, placebo controlled trial to investigate the effect of antibiotic prophylaxis on the rate of urinary tract infection in infants with prenatal hydronephrosis
2014, Journal of Urology
We determined the feasibility of a clinical trial of continuous antibiotic prophylaxis to prevent urinary tract infections in children with prenatal hydronephrosis.
We piloted a blinded, randomized, placebo controlled study of the urinary tract infection rate in infants with grades III-IV prenatal hydronephrosis at our institution between August 2010 and June 2013. Study exclusion criteria were grades I/II prenatal hydronephrosis, vesicoureteral reflux, duplication anomalies and age at randomization greater than 5 months. Prospectively collected feasibility data were obtained on eligibility, enrollment status, adherence to followup schedule, and medication and protocol compliance.
Of 301 screened patients 220 (73.1%) were ineligible for analysis and 2 (1%) missed the randomization window. Of the remaining 81 (26.9%) eligible patients 46 were enrolled (56.8%), 29 refused (39.5%) and consent is pending in 1 (1.2%). Reasons for declining participation included parental preference for or against continuous antibiotic prophylaxis and a lack of interest in participating in clinical research. Of 46 enrolled patients 29 (63%) completed the trial, 12 (26.1%) are still in followup and 5 (10.9%) withdrew. Of the 314 medication logs dispensed 263 were returned for a 95% mean medication compliance rate.
Based on the results of our pilot study a realistic recruitment rate for this group of patients is established, making a definitive trial of this topic feasible. However, due to the low number of eligible patients multicenter collaboration is critical to address the effect of continuous antibiotic prophylaxis on the urinary tract infection rate in this population. After study enrollment high medication and followup compliance can be expected.
Vesicoureteral reflux: Current trends in diagnosis, screening, and treatment
2012, European Urology
Vesicoureteral reflux (VUR) is present in approximately 1% of children in North America and Europe and is associated with an increased risk of pyelonephritis and renal scarring. Despite its prevalence and potential morbidity, however, many aspects of VUR management are controversial.
Review the evidence surrounding current controversies in VUR diagnosis, screening, and treatment.
A systematic review was performed of Medline, Embase, Prospero, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, clinicaltrials.gov, and the most recent guidelines of relevant medical specialty organizations.
We objectively assessed and summarized the published data, focusing on recent areas of controversy relating to VUR screening, diagnosis, and treatment.
The evidence base for many current management patterns in VUR is limited. Areas that could significantly benefit from additional future research include improved identification of children who are at risk for VUR-related renal morbidity, improved stratification tools for determining which children would benefit most from which VUR treatment option, and improved reporting of long-term outcomes of VUR treatments.
Renal Infection, Abscess, Vesicoureteral Reflux, Urinary Lithiasis, and Renal Vein Thrombosis
2012, Pediatric Surgery, 2-Volume Set: Expert Consult - Online and Print

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^☆: Supported by the New Children’s Hospital Fund, the Australian Kidney Foundation, and the National Health and Medical Research Council of Australia.

^☆☆: Reprint requests: Jonathan Craig, MBChB, Centre for Kidney Research, Clinical Sciences Building, PO Box 3515 Parramatta, NSW 2124, Australia.

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Original ArticlesAntibiotics for the prevention of urinary tract infection in children: A systematic review of randomized controlled trials☆,☆☆

Abstract

Section snippets

Inclusion Criteria

Literature Search

Trial Characteristics

Discussion

Pediatr Clin North Am

Lancet

Lancet

J Urol

Association between urinary symptoms at 7 years old and previous urinary tract infection [see comments]

Arch Dis Child

Symptomatic urinary tract infection in Australian preschool children: clinical features, microbiology, renal tract abnormalities and short-term outcomes

J Paediatr Child Health

Occurrence of renal scars in children after their first referral for urinary tract infection

BMJ

Morbidity, age and sex distribution, recurrences and renal scarring in symptomatic urinary tract infection in childhood

Kidney Int

Risk factors for recurrent urinary tract infection in preschool children

J Paediatr Child Health

Recurrent urinary tract infections in children

Pediatr Infect Dis

Sex differences in childhood urinary tract infection

Arch Dis Child

Original Articles
Antibiotics for the prevention of urinary tract infection in children: A systematic review of randomized controlled trials☆,☆☆