USI guidelines for the management of paediatric urinary tract infection

Contributors: -#Dr. MS Ansari (Professor) -#Dr. Ashwin P. Sekhar (Fellow) -*Dr. Chandra Singh (Professor) -+Dr. S.S. Joshi (Senior Consultant)

Affiliation: #Division of pediatric Urology Department of Urology and Renal Transplantation Sanjay Gandhi PGIMS, Luknow -226014 *Department of Urology The Christian Medical College, Vellore +Jaslok Hospital, Mumbai

Preamble In 30% of children with urinary tract anomalies, urinary tract infection (UTI) can be the first sign. If we fail to identify patients at risk, damage to the upper urinary tract may occur (1-11). Up to 85% of infants and children with febrile UTI have visible photon defects on technetium Tc 99–labeled dimercaptosuccinic acid (DMSA) scanning and 10–40% of these children have permanent renal scarring that may lead to poor renal growth, recurrent pyelonephritis, impaired glomerular function, early hypertension and end stage renal disease. Identifying children at risk of renal parenchymal damage and follow-up imaging after UTI may be challenging 12-15. It may be difficult to recognize UTI in children because the presenting symptoms and signs are non-specific, particularly in infants and children younger than 3 years (3,9-10). Collecting urine and interpreting results are not easy in this age group, so it may always be possible to unequivocally confirm the diagnosis. The guidelines have been developed with the aim of providing guidance on several aspects of UTI in infants and children from birth up to the age of 16 years. In these guidelines, we provide recommendations for the diagnosis, treatment, and imaging of children presenting with first or recurrent upper or lower urinary tract infections in infants and children based on evidence, and when this is lacking, based on expert consensus (2-9) . It aims to achieve more consistent clinical practice, based on accurate diagnosis and effective management. Who is it for?  Healthcare professionals  Infants and children from birth up to the age of 16 years with urinary tract infection  Their families and caregivers 1.0 Material and Methods Several guidelines dealing with specific subgroups of UTI are currently available, some of which are driven by economic and health care issues. The recommendations in 3 these guidelines were developed after a review of the literature from National institute for health and clinical excellence [NICE] guidelines, American Academy of Pediatrics [AAP] guidelines, European Society of Pediatric Urology (ESPU), Urological Clinic of America (UCNA) and a search of PubMed for UTI and newborn, infants, preschool, school, child, and adolescent 1-10,15. Special attention was given to publications made from Indian subcontinent as to make these recommendations aptly applicable to local needs and clinical circumstances (5-10, 18). A consensus decision was adopted when evidence was low. In these cases, all relevant papers and statements were discussed by all the authors until a consensus was achieved. 1.1 Classification The four widely used infection classification systems depend on the site, episode, symptoms and complicating factors. For acute treatment, the site and severity are the most important. (i) Classification according to site  Cystitis (lower urinary tract) – Inflammation of the urinary bladder mucosa with symptoms including burning micturition, frequency, urgency, malodorous urine, incontinence, haematuria and suprapubic pain. However, in newborns and infants, these symptoms are seldom present.  Pyelonephritis (upper urinary tract) – Diffuse pyogenic infection of the renal pelvis and parenchyma with symptoms including fever (38.8 0C) in addition to some symptoms of cystitis. But unlike adults, infants and young children may have nonspecific signs such as poor appetite, failure to thrive, lethargy, irritability, vomiting, or diarrhea 1-3 . (ii) Classification according to episode Classified as  First infection  Recurrent infection o Unresolved or Persistent 4 o Reinfection (1-3). (iii) Classification according to symptoms  Asymptomatic bacteriuria (ABU) indicates attenuation of uropathogenic bacteria by the host or colonisation of the bladder by nonvirulent bacteria that are incapable of activating a symptomatic response (no leucocyturia or symptoms). In patients with significant bacteriuria, leucocyturia can be present without any symptoms.  Symptomatic UTI includes irritative voiding symptoms, suprapubic pain (cystitis), fever, and malaise (pyelonephritis).  In patients with a neurogenic bladder and malodorous urine, it is difficult to distinguish between ABU and symptomatic UTI (6) . (iv) Classification according to complicating factors  Uncomplicated UTI is an infection in a patient with a morphologic and functionally normal upper and lower urinary tract, normal renal function and a competent immune system.  Complicated UTI occurs in newborns, in most patients with clinical evidence of pyelonephritis, and in children with known mechanical or functional obstruction or anomalies of the upper or lower urinary tract (1-4). 2. Diagnostic workup 2.1 Medical history The site, episode, symptoms, and complicating factors are identified by taking the patient’s history. This includes questions on primary (first) or secondary (recurring) infection, febrile or non-febrile UTIs, malformations of the urinary tract, previous operations, fluid intake and voiding habits, family history, whether there is constipation or the presence of lower urinary tract symptoms (LUTS), sexual history needs to be obtained in adolescents (1-5) . The following risk factors for UTI and serious underlying pathology should be recorded:  history of poor urine flow  history suggesting previous UTI or confirmed previous UTI 5  recurrent fever of uncertain origin  antenatally diagnosed renal abnormality  family history of vesicoureteric reflux (VUR) or renal disease  Loaded colon suggestive of constipation  history of spinal lesion/ surgery 2.2 Clinical signs and symptoms Fever may be the only symptom of UTI, especially in young children. Newborns with pyelonephritis or urosepsis can present with nonspecific symptoms (failure to thrive, jaundice, vomiting, hyperexcitability, lethargy, hypothermia, and sometimes without fever). Septic shock is unusual even with high fever, unless obstruction is present or the child is otherwise compromised. In older children, lower urinary tract symptoms include burning micturition, stranguria, frequency, urgency, malodorous urine, incontinence, haematuria, and suprapubic pain. Upper urinary tract symptoms include fever and flank pain. UTI in infancy may also be accompanied by a transient pseudohypoaldosteronism with profound hyponatraemia with or without hyperkalaemia (Table1) (1-5). 2.3 Physical examination A complete physical examination is required to exclude any other source of fever and especially if the fever has no apparent cause, UTI should be ruled out. Physical examination should search for signs of (1-10)  Palpable bladder  Palpable and painful kidney  Constipation  Stigmata of spina bifida or sacral agenesis spine and feet  Genital disorders (phimosis, labial adhesion, postcircumcision meatal stenosis, abnormal urogenital confluence, cloacal malformations, vulvitis, epididymoorchitis)  Measure temperature. 6 2.4 Clinical differentiation between acute pyelonephritis/upper urinary tract infection and cystitis/lower urinary tract infection  Infants and children who have bacteriuria and fever of 38°C or higher should be considered to have acute pyelonephritis/upper urinary tract infection.  Infants and children presenting with fever lower than 38°C with loin pain/tenderness and bacteriuria should also be considered to have acute pyelonephritis/upper urinary tract infection (1-10) .  All other infants and children who have bacteriuria but no systemic symptoms or signs should be considered to have cystitis/lower urinary tract infection (6-9) . 3. Urine sampling, analysis and culture  Infants and children with symptoms and signs suggestive of urinary tract Infection (UTI) should have a urine sample tested for infection.  Infants and children presenting with unexplained fever of 38°C or higher should have a urine sample tested within 24 hours.  Infants and children with an alternative site of infection should not have a urine sample tested. When infants and children with an alternative site of infection remain unwell, urine testing should be considered after 24 hours at the latest (2, 14-16) . 3.1Urine collection Before any antimicrobial agent is given, urine sampling must be performed. The technique used to obtain urine for urinalysis or culture affects the rate of contamination that in turn influences interpretation of the results, especially in early infancy (2-8) . A] Newborns, infants, and non–toilet-trained children In newborns, infants and non–toilet-trained children, there are three main methods for obtaining urine with varying contamination rates and invasiveness.  For clean-catch urine collection, the infant is placed in the lap of a parent or nurse holding a sterile foil bowl underneath the infant’s genitalia. This is time consuming and requires careful instructing of the parents. If not done properly 7 the contamination rates can go up to 26% in clean-catch urine compared with 1% in the (SPA) (1-3) .  Bladder catheterization may be an alternative to suprapubic aspiration (SPA) (vide infra) or when clean catch sample is not possible, although the rates of contamination are higher. The risk factors for a high contamination rate using this technique are patients <6 months of age, difficult catheterization and uncircumcised boys (6). Therefore, in children <6 months of age and uncircumcised boys, use of a new sterile catheter with each repeated attempt at catheterization may reduce contamination. Otherwise, SPA should be the method of choice. Catheterization is preferable in children with urosepsis when a permanent catheter may be considered in the acute phase (1-4) .  Suprapubic Aspiration (SPA) is the most sensitive method for obtaining an uncontaminated urine sample. Using ultrasound (US) to assess bladder filling simplifies the aspiration. Bladder puncture causes more pain than catheterization in infants <2 months of age. The eutectic mixture of Local Anesthetics, an emulsion containing a 1:1 mixture of lidocaine a prilocaine, can be used topically to reduce pain.  In an infant or child with a high risk of serious illness it is highly preferable that a urine sample is obtained; however, treatment should not be delayed if a urine sample is unobtainable (1-4). B] Toilet-trained children  In toilet-trained children, a clean voided midstream urine (MSU) sample has a good rate of accuracy. It is important to clean the genitalia beforehand to reduce the contamination rate. Contamination can be minimized by washing the genitalia with soap and water. Antiseptic washes and forced retraction of the prepuce are not advised. In this age group, clean catch voided urine, preferably midstream, has a sensitivity of 75–100% and a specificity of 57–100% (17).  If there is strong suspicion of upper UTI and for the differential diagnosis of sepsis, it is appropriate to obtain an adequate urine sample by catheterization or SPA (1-4). 8 C] Plastic bag collection  Plastic bag collection should be avoided irrespective of the age (3) . 3.2 Urine preservation  If urine is collected but cannot be cultured within 4 hours of collection, the sample should be refrigerated at 4 0C for 12 – 24 hours or preserved with boric acid immediately.  The manufacturer’s instructions should be followed when boric acid is used to ensure the correct specimen volume to avoid potential toxicity against bacteria in the specimen (1-3). 3.3 Urine testing  Dipsticks and microscopy are commonly used for urinalysis. Most dipsticks test for nitrite, leukocyte esterase, protein and blood. A dipstick test that is positive for leucocyte esterase and nitrite is highly sensitive for UTI. A test that is negative for leukocyte esterase and nitrite is highly specific for ruling out UTI (Table 2) (2, 14-16) .  Microscopy is used to detect pyuria and bacteriuria. Significant pyuria is defined as >10 leukocytes per mm3 in a fresh uncentrifuged sample, or >5 leukocytes per high power field in a centrifuged sample. Bacteriuria alone has a higher sensitivity than pyuria alone, although if both are positive, there is a high likelihood of UTI (Table 3) (1-3) .  For all diagnostic tests there will be a small number of false negative results; therefore, clinicians should use clinical criteria for their decisions in cases where urine testing does not support the findings (1-5,17). 3.4. Indication for urine culture Urine samples should be sent for culture:  in infants and children with a positive result for leukocyte esterase or nitrite  presence of pyuria and/or bacteriuria on urinalysis 9  in infants and children who are suspected to have acute pyelonephritis/upper urinary tract infection  in infants and children with recurrent UTI  in infants and children with an infection that does not respond to treatment within 24–48 hours, if no sample has already been sent and when clinical symptoms and dipstick tests do not correlate (1-10) . The classical definition of >105 CFU/ml of voided urine is still used to define significant UTI in adult women. However, the count can vary and be related to the method of specimen collection, diuresis and the duration and temperature of storage between collection and cultivation. The American Academy of Pediatrics (AAP) Guidelines on UTI suggests that the diagnosis should be based on the presence of both pyuria and at least 50,000 CFU/ml in a SPA sample (1,7). However, some studies have shown that in voided specimens, ≥10,000 organisms may indicate significant UTI. If urine is obtained by catheterization, 1000–50,000 CFU/ ml is considered positive in symptomatic patient and any counts obtained after SPA should be considered significant (Table 4) (1-5). (Level =2, Grade: A) Urine culture should be repeated if contamination is suspected, e.g., mixed growth of two or more pathogens, or growth of organisms that normally constitute the periurethral flora (lactobacilli in healthy girls; enterococci in infants and toddlers). The culture should also be repeated in situations where UTI is strongly suspected but colony counts are equivocal. 3.5. Laboratory tests for localizing UTI  Serum electrolytes and blood cell counts should be obtained for monitoring ill patients with febrile UTI.  C-reactive protein has a lower specificity for identifying patients with renal parenchymal involvement and it should not be used as a sole criterion to differentiate acute pyelonephritis/upper urinary tract infection from cystitis/lower urinary tract infection in infants and children. 10  Serum procalcitonin (>0.5 ng/ml; >2 severe sepsis) can be used as a reliable serum marker for identifying severity of sepsis.  In a severely ill child, blood cultures should be taken as well as ultrasonography (US) imaging of the urinary tract (1-3) . 4. Imaging tests for localizing UTI  Early ultrasonographic (USG) examination is indicated in children with febrile UTI and urosepsis to discriminate initially between complicated and uncomplicated UTI within 24 hrs. of diagnosis or if patient is not responding to antibiotics or still febrile after 24 hrs. of therapy. When this is not available or the diagnosis still cannot be confirmed, a dimercaptosuccinic acid (DMSA) scintigraphy scan is recommended (1-3, 7, 17-19). 5. Management 5.1 Initial Evaluation  The patient is examined for the degree of toxicity, dehydration and ability to retain oral intake.  The blood pressure should be recorded along with history regarding bowel and bladder habits.  The child is examined for features that suggest an underlying functional or urological abnormality.  Complete blood counts, serum creatinine and a blood culture should be done in infants and children with complicated UTI (1-3) . 5.2 Immediate Treatment  The patient’s age, features suggesting toxicity and dehydration, ability to retain oral intake and the likelihood of compliance with medication(s) help in deciding the need for hospitalization.  In febrile children with signs of UTI (clinical signs, positive dipstick and/or positive microscopy), antibiotic treatment should be initiated as soon as possible to eradicate the infection, prevent bacteraemia, improve clinical outcome, diminish 11 the likelihood of renal involvement during the acute phase of infection and reduce the risk of renal scarring.  Before any antibiotic therapy is started, a urine specimen should be obtained for urinalysis and urine culture. However, treatment should not be delayed waiting for the result of the urine culture.  In children with febrile UTI and no previous normal USG examination, USG of the urinary tract within 24 hours is advised to exclude obstructive uropathy, depending on the clinical situation (5-7) . (Level =2a, Grade: A) 5.3 Asymptomatic bacteriuria (ABU) In ABU without leucocyturia, antibiotic treatment should be avoided unless UTI causes problems or an operative procedure is planned. Screening for and treatment of ABU should be discouraged, irrespective of the method of urine sampling (1-3, 5-7) . (Level =3, Grade: B) 5.4 Febrile children: administration route  When choosing between oral and parenteral therapy, these factors should be considered: patient age, clinical suspicion of urosepsis, severity of illness, refusal of fluids, food, and/or oral medication, vomiting, diarrhea, noncompliance and complicated febrile UTI (e.g., upper tract dilatation).  As a result of the increased incidence of urosepsis and severe pyelonephritis in newborns and infants < 6 months of age, parenteral antibiotic therapy is recommended (Table 5) (1-10) .  Children less than 6 months of age and those with complicated UTI should be hospitalized and treated with parenteral antibiotics.  The choice of antibiotic should be guided by local sensitivity patterns. A thirdgeneration cephalosporin is preferred to initiate therapy. Therapy with a single daily dose of an aminoglycoside may be used in children with normal renal function. 12  Once the result of antimicrobial sensitivity is available, the treatment may be modified.  For pyelonephritis parenteral antibiotics for 72 hours until defervesecence, followed by oral antibiotics for 10 days. (Level =2a, Grade: A) 5.5 Duration of therapy in febrile urinary tract infection  Parenteral antibiotic therapy should be continued until the child is afebrile, after which oral antibiotics should be given.  If ambulatory (outpatient) therapy is chosen in late infancy, adequate surveillance, medical supervision and if necessary, adjustment of therapy must be guaranteed. In the initial phase of therapy, close contact with the family is advised.  In complicated UTI with uropathogens other than E coli, parenteral treatment with broad-spectrum antibiotics is preferred.  Temporary urinary diversion may be required in obstructive uropathy, depending on clinical status and/or response to antibiotic therapy.  A 7–14 day course of antibiotic therapy is sufficient UTI treatment (1-3, 5-7) . (Level =2a, Grade: A) 5.6 Antimicrobial agents Tables 6 lists the commonly used antimicrobial agents used in management of paediatric UTI. (1-10) 5.7 Supportive Therapy  During an episode of UTI, it is important to maintain adequate hydration. A sick, febrile child with inadequate oral intake or dehydration may require parenteral fluids.  Routine alkalization of the urine is not necessary.  Paracetamol is used to relieve fever; therapy with non-steroidal anti-inflammatory agents should be avoided. 13  A repeat urine culture is not necessary, unless there is persistence of fever and toxicity despite 72 hours of adequate antibiotic therapy (1-3, 5-7) . (Level =2, Grade: B) 6. Monitoring of urinary tract infection With successful treatment, urine usually becomes sterile after 24 hours, and leucocyturia normally disappears within 3–4 days. Normalization of body temperature can be expected within 24–48 h after the start of therapy in 90% of cases. In patients with prolonged fever and failing recovery, treatment-resistant uropathogens or the presence of congenital uropathy or acute urinary obstruction should be considered. Immediate ultrasonographic (USG) examination is necessary, if not performed initially as recommended. Procalcitonin (among other laboratory inflammatory parameters such as C-reactive protein and leukocyte count) can be used as a reliable serum marker for early prediction of renal parenchymal inflammation with a first febrile UTI. In patients with febrile UTI, serum electrolytes and blood cell counts should be obtained (1-3). 7. Evaluation after first UTI 7.1 Imaging tests The aim of investigations is to identify patients at high risk of renal damage, chiefly those below one year of age, and those with vesicoureteric reflux (VUR) or urinary tract obstruction. Evaluation includes ultrasonography, dimercaptosuccinic acid (DMSA) renal scan and voiding cystourethrogram (VCUG) performed judiciously (Figure 1) 1-3, 5, 15,18,19,29 (i) Ultrasound  An ultrasonogram (USG) provides information on kidney size, number and location, presence of hydronephrosis, urinary bladder anomalies and post-void residual urine. Renal and bladder USG is advised in all children with febrile UTI to exclude dilatation or anomalies of the upper and lower urinary tract if no improvement is seen within 24 hours because some conditions are life threatening. 14  It can be delayed in those with a previous normal USG examination, depending on the clinical situation.  Post void residual urine should be measured in toilet trained children to exclude voiding abnormalities. If pelvic USG shows filling of the rectum >30 mm, constipation must be considered (1-3, 5, and 7) . (Level =2, Grade: B)  (ii) Renal scintigraphy (DMSA)  DMSA scintigraphy is a sensitive technique for detecting renal parenchymal infection and cortical scarring. Changes in DMSA clearance during acute UTI indicate pyelonephritis or parenchymal damage and they correlate well with the presence of dilating reflux and the risk of further breakthrough infections and future renal scarring.  DMSA scanning can be used as a first-line diagnostic procedure based on observations that dilating vesicoureteric reflux (VUR) occurs in most children with an abnormal DMSA scan (19).  DMSA scan is best to be done after 4-6 months after UTI (2).  In top down approach DMSA scan is done first, if that shows abnormality then only a voiding cystourethrogram (VCUG) is prescribed (1-3, 5, 7,19) . (Level =2, Grade: B) (iii) Voiding Cystourethrogram (VCUG)  VCUG detects VUR and provides anatomical details regarding the bladder and the urethra. Follow-up studies in patients with VUR can be performed using direct radionuclide cystography (RNC).  VCUG is still the gold standard for the exclusion or confirmation of VUR. The radiation dose can be reduced (eight times lower) by using grid-controlled variable-rate pulsed fluoroscopy rather than continuous fluoroscopy. The radiation dose in children 10 years of age is approximately 0.1–0.55 mSv. Using 15 the techniques available for radiation protection, it is possible routinely to reduce the radiation dose below the lowest reference level valid for newborns.  VCUG is recommended 2-3 weeks after the UTI (1-3).  Performance of early VCUG in patients with proven sterile urine does not cause any significant morbidity. VCUG should be performed after UTI has been treated.  When a VCUG is performed, prophylactic antibiotics should be given orally for 3 days with VCUG taking place on the second day.  In conventional approach (i.e. Bottom up) VCUG is done first; DMSA scan is prescribed only if VUR is detected (29) . A simple algorithm for workup in cases of UTI is suggested through the figure 1 (1- 3, 5, 15, 18, 19, 29). (Level =2, Grade: B) 8. Prevention of recurrence 8.1 General  Children who have had a UTI should be encouraged to drink an adequate Amount of liquids (~40 ml/kg/day).  Children who have had a UTI should have ready access to clean toilets when required and should not be expected to delay voiding.  Bladder bowel dysfunction (BBD) and constipation should be addressed in infants and children who have had a UTI.  In children with VUR who are toilet trained, regular and volitional low pressure voiding with complete bladder emptying is encouraged. Double voiding ensures emptying of the bladder of post void residual urine.  Circumcision reduces the risk of recurrent UTI in infant boys, and might therefore have benefits in patients with high grade reflux (3,15) . (Level =4, Grade: 3) 8.2 Bladder and bowel dysfunction (BBD)  BBD describes a spectrum of lower urinary symptoms (LUTS) associated with fecal elimination issues that presents primarily by constipation and/or encopresis. 16  BBD is a risk factor for which every child with UTI should be screened at presentation. Correction of lower urinary tract dysfunction is important to decrease the rate of UTI recurrence.  If there are signs of BBD during infection-free intervals, further diagnosis and effective treatment are strongly recommended.  Treatment of constipation leads to a decrease in UTI recurrence.  Exclusion of BBD is therefore strongly recommended in any child with febrile and/or recurrent UTI, and, if present, treatment of BBD is necessary (27-28) . (Level =3, Grade: A) 8.3 Antibiotic prophylaxis Long-term, low dose, antibacterial prophylaxis is used to prevent recurrent, febrile UTI. The antibiotic used should be effective, non-toxic with few side effects and should not alter the growth of commensals or induce bacterial resistance. Antibiotic prophylaxis should not be routinely recommended in infants and children following first-time UTI (20- 25). 8.4 Indications and duration of Prophylaxis The indications and duration of prophylaxis depend on patient’s age and presence or absence of VUR. Antibiotic prophylaxis is recommended for patients with,  UTI below 1-yr of age, while awaiting imaging studies  VUR, all grades in infants less than 2 years, dilating VUR, Grade 3-5 in 2-5 yrs  Recurrent febrile UTI (3 or more episodes in a year) even if the urinary tract is normal (3,5, 20-27) . (Level =2, Grade: 2) 8.5 Breakthrough UTI on Prophylactic Antibiotics Breakthrough UTI usually results either from poor compliance or associated voiding dysfunction. The UTI should be treated with appropriate antibiotics. A change of the medication being used for prophylaxis is usually not necessary. There is no role for cyclic therapy, where the antibiotic used for prophylaxis is changed every 6-8 weeks. 8.6 Prophylaxis not indicated 17 Antibiotic prophylaxis is not advised in patients with urinary tract obstruction (e.g., posterior urethral valves), urolithiasis and neurogenic bladder and in patients on clean intermittent catheterization. In these cases, the primary cause needs to be addressed first. Asymptomatic bacteriuria in infants and children should not be treated with prophylactic antibiotics (1-3, 6- 8) . (Level =4, Grade: C) . 9. Follow-up  When results are satisfactory, a follow-up outpatient appointment is not routinely required. Parents or carers should be informed of the results of all the investigations in writing.  Infants and children who have recurrent UTI or abnormal imaging results should be assessed by a paediatric urologist.  Assessment of infants and children with renal parenchymal defects should include height, weight, blood pressure and routine testing for proteinuria (1-7,31-32). Infants and children with a minor, unilateral renal parenchymal defect do not need long-term follow-up unless they have recurrent UTI or family history or lifestyle risk factors for hypertension.  Infants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure and/or proteinuria (random spot protein creatinine ratio >0.2 suggests significant proteinuria) should receive monitoring and appropriate management by a paediatric nephrologist to slow the progression of chronic kidney disease.  Infants and children who are asymptomatic following an episode of UTI should not routinely have their urine re-tested for infection (No screening urinalysis or culture).  Asymptomatic bacteriuria is not an indication for follow-up (1-7, 31-32). 10. Information and advice for children, young people and parents or carers  Healthcare professionals should ensure that when a child or young person has been identified as having a suspected UTI, they and their parents or carers get 18 appropriate information about the need for treatment, the importance of completing any course of treatment and advice about prevention and possible long-term management.  Healthcare professionals should ensure that children and their parents or carers are aware of the possibility of a UTI recurring and understand the need for vigilance and to seek prompt treatment from a healthcare professional for any suspected reinfection (33).  Healthcare professionals should offer children and young people and/or their parents or carers appropriate advice and information on: o prompt recognition of symptoms o urine collection, storage and testing o appropriate treatment options o prevention o the nature of and reason for any urinary tract investigation o prognosis o reasons and arrangements for long-term management if required 11. SUMMARY  Urinary tract infection is one of the most common bacterial infections in children.  Since UTI can present with vague clinical complaints, UTI should be considered in any infant or child presenting with fever without an obvious source of infection.  Prompt diagnosis and early therapy are crucial in the prevention of longterm UTI related complications.  Diagnosis of UTI requires both a urinalysis to confirm pyuria and the presence of at least >50,000 colony forming units/mL of a single uropathogen in a properly collected urine specimen. However, some studies have shown that in voided specimens, ≥10,000 organisms may indicate significant UTI in symptomatic children. 19  Infants with UTI should be imaged with renal and bladder ultrasound (USG-KUB) and VCUG. While in child greater than one year of age VCUG is to be done only when USG–KUB shows structural changes.  A top down approach (i.e. DMSA scan first) seems to be simpler and appealing since it avoids the need of catheterization and serial imaging during filling and voiding.  A 7–14-day course of antibiotic therapy is usually sufficient for the treatment.  Continuous antibiotic prophylaxis is advised in:  UTI below 1-yr of age, while awaiting imaging studies,  VUR  Recurrent febrile UTI (3 or more episodes in a year) even if the urinary tract is normal.  Bladder bowel dysfunction BBD is a risk factor for which every child with UTI should be screened at presentation 20 Abbreviations UTI: Urinary tract infection USG: Ultrasonography KUB: Kidney ureter Bladder DMSA: Dimercaptosuccinic acid VCUG: Voiding Cystourethrogram NICE: National institute for health and clinical excellence AAP: American Academy of Pediatrics ESPU: European Society of Pediatric Urology (ESPU) UCNA: Urological clinics of North America 2015 21

References

1. Committee on Quality Improvement Subcommittee on Urinary Tract Infection. Practice parameter. The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Pediatrics. 1999; 103(4 Pt 1):843–852. 2. Deader R, Tiboni SG, Malone PS, Fairhurst J. Will the implementation of the 2007 National Institute for Health and Clinical Excellence (NICE) guidelines on childhood urinary tract infection (UTI) in the UK miss significant urinary tract pathology? 3. Urinary Tract Infections in Children: EAU/ESPU Guidelines. Raimund Stein , Hasan S. Dogan, Piet Hoebeke , Radim Kocˇvara , Rien J.M. Nijman, Christian Radmayr , Serdar Tekgu¨l . EUROPEAN UROLOGY 67 (2015) 546–558 4. Quigley R. Diagnosis of urinary tract infections in children. Curr Opin Pediatr. 2009; 21(2):194–198. 5. V. Kumar. Revised Statement on Management of Urinary Tract Infections. Indian Pediatr 2011;48:709-711 6. Mak RH, Kuo HJ. Pathogenesis of urinary tract infection: an update. Curr Opin Pediatr. 2006; 18(2):148–152. 7. Bitsori M, Galanakis E. Pediatric urinary tract infections: diagnosis and treatment. Expert Rev Anti Infect Ther. 2012; 10(10):1153–1164. Updated American Academy of Pediatrics Guidelines for initial UTI diagnosis and management. 8. 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(3):595–610. 9. Ristola MT, Hurme T. NICE Guidelines Cannot Be Recommended for Imaging Studies in Children Younger Than 3 Years with Urinary Tract Infection. Eur J Pediatr Surg. 2014 22 10. Mishra OP, Abhinay A, Prasad R. Urinary infections in children. Indian J Pediatr. 2013; 80(10):838–843. 11. Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics. 2010; 126(6):1084–1091. 12. Chowdhury P, Sacks SH, Sheerin NS. Minireview: functions of the renal tract epithelium in coordinating the innate immune response to infection. Kidney Int. 2004; 66(4):1334–1344. 13. Faust WC, Diaz M, Pohl HG. Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature. The Journal of urology. 2009; 181(1):290–297. 14. Montini G, Tullus K, Hewitt I. Febrile urinary tract infections in children. N Engl J Med. 2011; 365(3):239–250 15. Hillary L. Copp, Bogdana Schmidt Urol Clin North Am. 2015 November ; 42(4): 519–526. 16. Van Howe RS. Effect of confounding in the association between circumcision status and urinary tract infection. J Infect. 2005; 51(1):59–68. 17. María Luisa Herreros, Alfredo Tagarro, MD PhD, Araceli García-Pose ei al. Paediatr Child Health. 2015 Aug-Sep; 20(6): 30–32. 18. M. S. Ansari, Halil Suat Ayyildiz, and V. R. Jayanthi. Is voiding cystourethrogram necessary in all cases of antenatal hydronephrosis? Indian J Urol. 2009 OctDec; 25(4): 545–546. 19. Pohl HG, Belman AB. The “top-down” approach to the evaluation of children with febrile urinary tract infection. Adv Urol. 2009:783409. 20. Chesney RW, Carpenter MA, Moxey-Mims M, Nyberg L, Greenfield SP, Hoberman A, Keren R, Matthews R, Matoo TK. Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR): background commentary of RIVUR investigators. Pediatrics. 2008; 122(Suppl 5):S233–239. 23 21. Brandstrom P, Esbjorner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial in children: III. Urinary tract infection pattern The Journal of urology. 2010; 184(1):286–291. 22. Brandstrom P, Neveus T, Sixt R, Stokland E, Jodal U, Hansson S. The Swedish reflux trial in children: IV. Renal damage J Urol. 2010; 184(1):292–297 23. Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014; 370(25):2367–2376. 24. Investigators RT, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. The New England journal of medicine. 2014; 370(25):2367–2376. Beetz R. May we go on with antibacterial prophylaxis for urinary tract infections? Pediatr Nephrol. 2006; 21 25. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006; 117(3):626–632. 26. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, Hodson EM, Carapetis JR, Cranswick NE, Smith G, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009; 361(18):1748–1759 27. 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 : the journal of the American Medical Association. 2007; 298(2):179–186. 28. Van Batavia JP, Ahn JJ, Fast AM, Combs AJ, Glassberg KI. Prevalence of urinary tract infection and vesicoureteral reflux in children with lower urinary tract dysfunction. The Journal of urology. 2013; 190(4 Suppl):1495–1499. 29. Chase J, Austin P, Hoebeke P, McKenna P. The management of dysfunctional voiding in children: a report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2010; 183(4):1296–1302. 30. Madden-Fuentes RJ, McNamara ER, Lloyd JC, Wiener JS, Routh JC, Seed PC,Ross SS. Variation in definitions of urinary tract infections in spina bifida patients: a systematic review. Pediatrics. 2013; 132(1):132–139 31. Fidan K, Kandur Y, Buyukkaragoz B, Akdemir UO, Soylemezoglu O. Hypertension in pediatric patients with renal scarring in association with vesicoureteral reflux. Urology. 2013; 81(1):173–177. 32. Jacobson SH, Eklof O, Lins LE, Wikstad I, Winberg J. Long-term prognosis of post-infectious renal scarring in relation to radiological findings in childhood–a 27-year follow-up. Pediatr Nephrol. 1992; 6(1):19–24. 33. Cost and Utlization Project Kids’ Inpatient Database.; 2013