Urinary tract infection in children Evidence update  Ihab Sakr Shaheen  Consultant Paediatric Nephrologist  Honorary senior lecturer, Glasgow University, UK

Why UTI?  IT CRIES  Dr Fahd

UTI has been aggressively investigated ? Focus on 0-36 moths old, first UTI

Vesico-ureteric reflux VUR Recurrent UTI/so prophylaxis ab Scar/impaired renal function

Aggressive radiological investigations and prophylaxis antibiotic use following UTI has been mainstay of clinical practice for decades

Objectives  Diagnosis  Investigation and management of VUR  Prophylaxis antibiotic  Surgical intervention  Imaging as per NICE/AAP  Glasgow data  High risk group  Recommendations  To take home

Prevalence  In a meta-analysis of 14 studies of prevalence of UTI is 5% among febrile children 0-24 months without obvious source So it is a common childhood disease

Diagnosis  Challenging, non specific symptoms  Neonates present with fever, vomiting, failure to thrive or overt sepsis.  Any child younger than 3 months with pyrexia of >38°C without any other focus for the temperature should always be checked for a urinary tract infection.  Infants and young children children with fever and abdominal pain  Older children with secondary wetting and urinary symptoms

Diagnosis  In small children always try to obtain the urine sample with suprapubic aspiration or bladder catheterisation If this is not possible then keep in mind the high risk of contaminated samples  A bacterial number of > 10 5 CFU/ml is useful to define a UTI but a proportion of true infections have lower bacterial numbers specially with different collecting methods

 Leucocyturia has a high sensitivity but low specificity in diagnosing a UTI  A positive nitrite test in a freshly voided sample has a low sensitivity but high specificity  Always aim to make a level diagnosis of a UTI – acute pyelonephritis, cystitis or asymptomatic bacteriuria (ABU)

VUR Is VUR common only in UTI patients?

 Chimpanzees have VUR when young but it disappear when the animals grow  10% dogs have VUR  All rats have VUR  50% of rabbits have VUR

In human  Prevalence of VUR in human is 1-2%, in few studies it has been reported as high as 25% in  Data on the prevalence of VUR among children without history of UTI do not exist.  The natural history of VUR ( grade I,II,III) is spontaneous resolution at a rate of 13% per year

VUR disappear spontaneously  Resolution in 2.4 years follow up: Grade I VUR 92.3% Grade II VUR  Dilating VUR ( III-V)10 years follow up: 73% VUR disappeared or changed to grade I VUR is a physiological finding which disappears as the child grows Huang etal, ped neph 1995;9:879-83

Chand etal, J Uro, 2003

Radiation dose ImagingEffective dose (mSV) MCUG/VCUG DMSA CXR0.03

Now…. We agree that VUR diagnosis by MCUG is not the task we should try to achieve After first febrile UTI with normal USS What about prophylaxis antibiotics?

Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children without VUR, from random-effects modeling. S. Maria E. Finnell et al. Pediatrics 2011;128:e749-e770 ©2011 by American Academy of Pediatrics

Recurrence of Pyelonephritis/Febrile UTI Among Children 2 to 24 Months of Age With VUR of Any Grade with and without use of prophylaxis antibiotics

S. Maria E. Finnell et al. Pediatrics 2011;128:e749-e770 ©2011 by American Academy of Pediatrics

There was no significant difference in rates of recurrence of pyelonephritis for children 2 to 24 months of age with VUR( of any grade)/without VUR who received antimicrobial agents and those who did not

VUR and surgical intervention  Only 1 RCT has compared surgical intervention for VUR with placebo and… Only difference was found in girls > 1 year who show decrease in the number of febrile UTIs Insufficient data to show whether and for whom such intervention may be helpful

Long-term consequences of VUR The link between VUR discovered after the first UTI and subsequent htn/ESRD remains not clear due to absence of longitudinal studies

AAP reviewed guidelines First-time UTI Age 2–24 months Ultrasound scan during acute infection No if responding to treatment Ultrasound scan within 6 weeks of infection Yes DMSA scan 4–6 months after acute infection Not discussed in guideline MCUG Consider, if ultrasound abnormal Antibiotic prophylaxis Only if evidence of grade V vesicoureteric reflux Summary of American Academy of Paediatrics guidelines on investigation and management of first-time urinary tract (UTI) infection

Summary of NICE guidelines Typical infectionAtypical infection* Age <6 months Ultrasound scan during acute infection No if responding to treatmentYes Ultrasound scan within 6 weeks of infection YesNo DMSA scan 4–6 months after acute infection NoYes Micturating cystourethrogram (MCUG) Consider, if ultrasound abnormalYes Antibiotic prophylaxis No Age 6 months to 3 years Ultrasound scan during acute infection NoYes Ultrasound scan within 6 weeks of infection No DMSA scan 4–6 months after acute infection NoYes MCUG NoConsider Antibiotic prophylaxis No Age >3 years Ultrasound scan during acute infection NoYes Ultrasound scan within 6 weeks of infection No DMSA scan 4–6 months after acute infection No MCUG No Antibiotic prophylaxis No

Effect of these guidelines

Glasgow data  Review MCUG results for 3 years post NICE guidelines ( 1 st June st May2011)  Renal USS and DMSA findings  Clinical Follow up from June 2008 for a minimum of 2 years ( 2-5 years) Recurrent UTI Surgical referral/intervention Further imaging

Renal abnormalities detected following renal ultrasound..

Glasgow data  75% of our MCUG reported normal  Only 4 cases ? out of 154 MCUG done suspected PUV but cystoscopy was normal ( suboptimal images), 1 has PUV  Abnormal MCUG is mainly VUR  Abnormal urethra during MCUG needs more attention  F/H ( 50% of scarred kidney has positive F/H), dysfunctional voiding and recurrent UTI would be better factors for the outcome than just presence of VUR in MCUG

so  No diagnosis  No treatment where should we shift our focus?

High risk group  Poor urinary stream  Antenatally-diagnosed renal abnormality  Abnormal USS  Family history of vesico-ureteric reflux (VUR), recurrent UTI, scarred kidneys or other renal disease

High risk group  Dysfunctional voiding  Enlarged bladder  Evidence of spinal lesion

Recommendations  USS if no response to treatment after 48 hrs  USS at 6 weeks post infection  MCUG if abnormal USS and discuss with radiologist/urologist  DMSA in atypical infection, positive family history  Refer girls with recurrent febrile UTI for Deflux after discussing with family and your local urologist

Recommendations  Cystitis treatment should typically be given for 2-4 days  Children with a cystitis should be treated with a narrow spectrum antibiotics e.g. Trimethoprim or Nitrofurantoin  Children with Asymptomatic Bacteriuria should not routinely be treated with antibiotics

Recommendations  Circumcision is protecting boys specially those with renal anomalies from recurrent febrile UTI  Children with an acute pyelonephritis will need broad spectrum empiric coverage related to local resistance patterns  Prophylaxis antibiotic could be beneficial in cystitis and ASB

To take home?  8 year old girl has been suffering from day time wetting for the last 6 months. She is dry during the night. No past medical history of note. No family history of enuresis. She does not have urgency or frequency. Her wetting is always happening few minutes after she passes urine. Urinalysis shows WBCs Urine culture shows contaminated growth at time of referral  What radiological investigations would you do?  What is your diagnosis ?

To take home  HISTORY fluid, constipation, bladder diary  Dysfunctional voiding in older children with recurrent UTI and incomplete bladder emptying  Be selective with MCUG/surgical intervention  Talk to your radiology and urology colleagues  Get annual report from your local microbiology lab for resistance antibiotics and discuss with them

To take home Do not chase VUR as it is not a disease, MCUG is a bad test to do in most cases with first febrile UTI unless high risk Focus on history to be selective in investigating high risk cases If you decide to use antibiotic: rotate ab/talk to your micro lab/be honest with family about effectiveness of ab No perfect diagnostic algorithm exists

Thank you