A study of antibiotic susceptibility pattern of uropathogens in a tertiary care hospital in Greece showed that E. coli was responsible for about 70% of UTI . The prevalence of E. coli isolates resistant to ampicillin was 50%. Marcus et al. reviewed the UTI pathogens and their antibiotic susceptibility in Schneider Children's Medical Center of Israel from 2001 to 2005. Of the 355 culture-proven UTI episodes, 26 (6.2%) were due to Enterococcus spp., and the remaining 333 (93.8%) to Gram-negative bacteria, mainly E. coli, Klebsiella spp., and Pseudomonas aeruginosa. The Gram-negative isolates showed 24, 7, and 5% resistance to first-generation, second-generation, and third-generation cephalosporins, respectively. There has been no significant difference in the outcome of children with UTI due to extended spectrum β-lactamases (ESBL)-producing uropathogens compared with those with non-ESBL-producing uropathogens [27▪].
When and which imaging studies to obtain for evaluation of a child with UTI still remain controversial. The main question fueling the debate is the relevance of VUR in the causal pathway between UTI and renal scarring. Based on the answer to this question, two approaches have evolved: ‘top-down’ and ‘bottom-up’ . The ‘top-down’ approach focuses on kidney involvement during UTI with a goal of ruling in or out acute pyelonephritis, renal dysplasia, or acquired renal scarring. Proponents of ‘top-down’ approach recommend the use of renal bladder ultrasonography (RBUS) and dimercaptosuccinic acid (DMSA) renal scan first. Vesicoureterogram (VCUG) is performed only if renal involvement is observed. The ‘bottom-up’ approach focuses on bladder involvement during UTI with a goal of diagnosing VUR; therefore, VCUG is obtained first. The NICE guidelines discourage routine imaging of all children after a first UTI . RBUS is reserved for only atypical or recurrent UTI or for children less than 6 months of age. DMSA is recommended only in children less than 3 years of age with atypical or recurrent UTI and it is performed 4–6 months after UTI. The new AAP guidelines also do not recommend routine imaging studies for first UTI in children aged between 2 and 24 months. However, it is recommended that febrile infants with first UTI should have RBUS to detect anatomic abnormalities that may require further evaluation [7▪▪]. Thus, VCUG and DMSA are no longer routine investigations after first febrile UTI, as evidence supports that the yield of actionable findings from imaging is relatively low [7▪▪].
Ultimately, ‘an ounce of prevention is better than a pound of cure.’ The role of prophylactic antibiotics, cranberry juice, management of dysfunctional elimination syndrome, probiotics, and circumcision in preventing UTI is discussed below.
Prophylactic antibiotics have been used on the assumption that they prevent recurrent UTI, renal damage, or both in young children with UTI with or without VUR. Several studies have discredited this assumption. Moreover, chronic antibiotic use has a number of disadvantages for the individual as well as the population as a whole. The NICE guidelines do not recommend routine antibiotic prophylaxis in infants and children after first UTI. The recent AAP guidelines also do not recommend prophylactic antibiotics after first UTI in children aged 2–24 months [7▪▪]. Islek et al. followed infants (n = 84) with prenatal ureteropelvic junction obstruction without antibiotic prophylaxis for 12–24 months and none of the patients had UTI or renal scar during the follow-up period.
There is resurgence in the use of cranberry products to prevent recurrence of UTI. The proposed mechanism of action is inhibition of uropathogenic E. coli at the uroepithelium. In a recent systematic review of published randomized clinical trials, Wang et al. found that consumption of cranberry products may protect against UTIs in certain populations. However, they concluded on a cautious note, based on the substantial heterogeneity across trials. Stapleton et al. randomized 176 women to two arms (120 to cranberry juice and 56 to placebo) and followed them for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P = 0.82). The adjusted hazard ratio for UTI in the cranberry juice group vs. the placebo group was 0.68 (95% confidence interval 0.33–1.39; P = 0.29). They concluded that, though cranberry juice did not significantly reduce UTI risk compared with placebo, the potential protective effect observed warrants confirmation in larger, well-powered studies. Salo et al.[36▪] randomized 263 children with UTI to receive either cranberry juice (n = 129) or placebo (n = 134) for 6 months and followed them for a year in seven Finnish hospitals. The intervention did not significantly reduce the number of children who experienced a recurrence of UTI.
Dysfunctional elimination syndrome is a known cause of UTI. The syndrome comprises of inability to effectively empty the bladder, incontinence, constipation, and other voiding symptoms. Biofeedback therapy has been helpful in improving voiding symptoms in children with dysfunctional voiding. The pooled estimate from 27 studies reviewed by Desantis et al. showed 83% (95% confidence interval 76–86%) improvement in UTI with biofeedback therapy in children less than 18 years of age. The authors concluded that well-designed trials are needed to evaluate the effectiveness of biofeedback in prevention of UTI in children.
The use of probiotics to prevent UTI is being explored. Probiotics contain a live microorganism given to confer health benefit to the host without causing infection or untoward effects. The use of probiotics in prevention of bacterial infections has received mixed reviews. Probiotics work by displacing pathogenic bacteria from the gut as well as boosting the innate immunity of the gut. In a prospective randomized study comparing conventional antibiotics and probiotics in treating children with primary VUR, the incidence of recurrent UTI was comparable in both groups of children [38,39]. In an in-vitro study, Storm et al.[40▪] found that ‘Mutaflor’ (a probiotic containing E. coli Nissle 1917) had bactericidal effect against a wide range of uropathogens. They concluded that probiotics may be effective in preventing and eliminating the colonization of pathogenic bacteria in the gut and that such a reduction in the fecal load of uropathogens will translate to a reduction in the incidence of recurrence of UTI.
Will the cutting of the foreskin become the cutting-edge of prevention of UTI in boys? Previous studies have established an association between circumcision and reduced risk of UTI in boys. However, the number of circumcisions needed to prevent one UTI is reported to be about 111 in the general population [10▪▪]. Is this a cost-effective strategy for the general population or should it be reserved for boys at high risk of UTI? The AAP recently highlighted the benefits of male circumcision and concluded that the health benefits of newborn male circumcision outweigh the risks . They encouraged providers to explain the benefits and risks of circumcision to parents and to leave the final decision for or against circumcision to the parents.
With high suspicion for UTI and early treatment, UTI complications including renal scarring could be avoided. Patients and their families should be given the message that UTI is an acute infection and, with appropriate and timely treatment, UTI usually resolves with no untoward consequences. However, certain individuals may have a predilection for recurrences and occasionally this is a marker of congenital renal abnormalities or urinary tract obstruction. These conditions may be screened for with RBUS . Further research is needed to elucidate and validate host factors and genetic variations predisposing to renal scarring. These factors should be considered in future clinical practice guidelines for UTI in order to further avoid unnecessary invasive procedures. Providers using current guidelines should endeavor to collect practice-based evidence to validate and inform future guidelines.
Papers of particular interest, published within the annual period of review, have been highlighted as:
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 155–156).
1▪. Copp HL, Shapiro DJ, Hersh AL. National ambulatory antibiotic prescribing patterns for pediatric urinary tract infection, 1998–2007. Pediatrics 2011; 127:1027–1033.
The study describes the burden of ambulatory UTI in children in the United States and inappropriate antibiotics prescription practices for UTI management.
2. Deluca FG, Fisher JH, Swenson O. Review of recurrent urinary tract infections in infancy and early childhood. N Engl J Med 1963; 268:75–77.
3. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999; 103:843–852.
4. Smellie JM, Barratt TM, Chantler C, et al.
Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial. Lancet 2001; 357:1329–1333.
5. Routh JC, Bogaert GA, Kaefer M, et al. Vesicoureteral reflux: current trends in diagnosis, screening, and treatment. Eur Urol 2012; 61:773–782.
7▪▪. Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011; 128:595–610.
The new AAP practice guidelines for the management of UTI in children between 2 and 24 months of age.
8▪. Beetz R. Evaluation and management of urinary tract infections in the neonate. Curr Opin Pediatr 2012; 24:205–211.
A comprehensive review of management of UTI in neonates.
9. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli
. Nat Rev Microbiol 2004; 2:123–140.
10▪▪. Montini G, Tullus K, Hewitt I. Febrile urinary tract infections in children. N Engl J Med 2011; 365:239–250.
A great review of management of UTI in children and the pathogenesis of UTI.
11. Ragnarsdottir B, Lutay N, Gronberg-Hernandez J, et al. Genetics of innate immunity and UTI susceptibility. Nat Rev Urol 2011; 8:449–468.
12▪. Storm DW, Patel AS, Horvath DJ Jr, et al. Relationship among bacterial virulence, bladder dysfunction, vesicoureteral reflux and patterns of urinary tract infection in children. J Urol 2012; 188:236–241.
A detailed description of the complex interplay between host and bacteria in the pathogenesis of UTI.
13. Storm DW, Patel AS, Koff SA, Justice SS. Novel management of urinary tract infections. Curr Opin Urol 2011; 21:328–333.
14. Cheng CH, Tsau YK, Kuo CY, et al. Comparison of extended virulence genotypes for bacteria isolated from pediatric patients with urosepsis, acute pyelonephritis, and acute lobar nephronia. Pediatr Infect Dis J 2010; 29:736–740.
15▪. Cheng CH, Lee YS, Tsau YK, Lin TY. Genetic polymorphisms and susceptibility to parenchymal renal infection among pediatric patients. Pediatr Infect Dis J 2011; 30:309–314.
The study highlights genetic susceptibility to UTI.
16▪▪. Salo J, Ikaheimo R, Tapiainen T, Uhari M. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics 2011; 128:840–847.
An important contribution to the understanding of the role of UTI in chronic kidney diseases.
17. Craig JC, Williams GJ. Denominators do matter: it's a myth – urinary tract infection does not cause chronic kidney disease. Pediatrics 2011; 128:984–985.
18▪. Cheng CH, Hang JF, Tsau YK, Lin TY. Nephromegaly is a significant risk factor for renal scarring in children with first febrile urinary tract infections. J Urol 2011; 186:2353–2357.
The study points out nephromegaly during acute UTI as a predictor of renal scar formation.
19▪. Lee YJ, Lee JH, Park YS. Risk factors for renal scar formation in infants with first episode of acute pyelonephritis: a prospective clinical study. J Urol 2012; 187:1032–1036.
The study describes VUR as an independent risk factor for renal scar formation.
20▪. Zaffanello M, Tardivo S, Cataldi L, et al. Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms. Pediatr Nephrol 2011; 26:1017–1029.
An important overview of the role of genetics in the development of renal scar formation after UTI.
21. Akil I, Ozkinay F, Onay H, et al. Assessment of Toll-like receptor-4 gene polymorphism on pyelonephritis and renal scar. Int J Immunogenet 2012; 39:303–307.
22. Powell HR, McCredie DA, Ritchie MA. Urinary nitrite in symptomatic and asymptomatic urinary infection. Arch Dis Child 1987; 62:138–140.
23▪. Beetz R, Westenfelder M. Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents 2011; 38:42–50.
The study stresses the importance of basing empiric treatment of UTI on local pattern of antibiotic susceptibility of uropathogens.
24▪▪. Bocquet N, Sergent Alaoui A, Jais JP, et al. Randomized trial of oral versus sequential IV/oral antibiotic for acute pyelonephritis in children. Pediatrics 2012; 129:e269–275.
An important contribution to validating the use of oral antibiotics in the management of UTI.
25. Mantadakis E, Tsalkidis A, Panopoulou M, et al. Antimicrobial susceptibility of pediatric uropathogens in Thrace, Greece. Int Urol Nephrol 2011; 43:549–555.
26. Marcus N, Ashkenazi S, Samra Z, et al. Community-acquired enterococcal urinary tract infections in hospitalized children. Pediatr Nephrol 2012; 27:109–114.
27▪. Tratselas A, Iosifidis E, Ioannidou M, et al. Outcome of urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children. Pediatr Infect Dis J 2011; 30:707–710.
Clinical outcome of UTI was independent of production of beta-lactamase in uropathogens.
28. Pennesi M, L’Erario I, Travan L, Ventura A. Managing children under 36 months of age with febrile urinary tract infection: a new approach. Pediatr Nephrol 2012; 27:611–615.
29▪▪. Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med 2011; 165:1027–1032.
A validation of restrictive approach to imaging studies after UTI; an experience of a US-based hospital before the new AAP recommendations.
30▪. Tsai JD, Huang CT, Lin PY, et al. Screening high-grade vesicoureteral reflux in young infants with a febrile urinary tract infection. Pediatr Nephrol 2012; 27:955–963.
A validation of ‘top-down’ approach in assessing renal damage after UTI.
31. Hannula A, Venhola M, Perhomaa M, et al. Imaging the urinary tract in children with urinary tract infection. Acta Paediatr 2011; 100:e253–e259.
32. Lee JH, Kim MK, Park SE. Is a routine voiding cystourethrogram necessary in children after the first febrile urinary tract infection? Acta Paediatr 2012; 101:e105–e109.
33. Islek A, Guven AG, Koyun M, et al. Probability of urinary tract infection in infants with ureteropelvic junction obstruction: is antibacterial prophylaxis really needed? Pediatr Nephrol 2011; 26:1837–1841.
34. Wang CH, Fang CC, Chen NC, et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2012; 172:988–996.
35. Stapleton AE, Dziura J, Hooton TM, et al. Recurrent urinary tract infection and urinary Escherichia coli
in women ingesting cranberry juice daily: a randomized controlled trial. Mayo Clin Proc 2012; 87:143–150.
36▪. Salo J, Uhari M, Helminen M, et al. Cranberry juice for the prevention of recurrences of urinary tract infections in children: a randomized placebo-controlled trial. Clin Infect Dis 2012; 54:340–346.
An important clinical trial on the role of cranberry products on prevention of UTI in children.
37. Desantis DJ, Leonard MP, Preston MA, et al. Effectiveness of biofeedback for dysfunctional elimination syndrome in pediatrics: a systematic review. J Pediatr Urol 2011; 7:342–348.
38. Lee SJ, Shim YH, Cho SJ, Lee JW. Probiotics prophylaxis in children with persistent primary vesicoureteral reflux. Pediatr Nephrol 2007; 22:1315–1320.
39. Yang SS, Chiang IN, Lin CD, Chang SJ. Advances in nonsurgical treatments for urinary tract infections in children. World J Urol 2012; 30:69–75.
40▪. Storm DW, Koff SA, Horvath DJ Jr, et al. In vitro analysis of the bactericidal activity of Escherichia coli
Nissle 1917 against pediatric uropathogens. J Urol 2011; 186:1678–1683.
A proof-of-concept study on the efficacy of probiotics to prevent recurrent UTI.
41. American Academy of Pediatrics Task Force on Circumcision. Male circumcision. Pediatrics 2012; 130:e756–e785.