URINARY TRACT INFECTION AND VESICO-URETERIC REFLUX IN CHILDHOOD Dr Lynster Liaw Penang Hospital
UTI
UTI: Epidemiology • comprises 5% febrile illnesses in early childhood • prevalence - 1.4/1000 newborns • 2.1% girls, 2.2% boys will get it before age 2 years • uncircumcised > circumcised boys • E coli in 75 - 90% of all infections • others: Klebsiella, Proteus
Terminology • definition (UTI): = growth of bacteria in the urine and presence of suggestive clinical features • acute pyelonephritis (upper tract): infection of the renal parenchyma • acute cystitis (lower tract): infection limited to lower urinary tract
Asymptomatic bacteriuria • Presence of bacteria in repeated samples of urine in a well, asymptomatic child. • Usually detected on routine investigations.
Why important? • sign of underlying UT abnormality • significant morbidity / mortality • long term risks of - hypertension - end stage renal failure
Pathogenesis • Pathogenic bacteria from gut flora colonises periurethral area → ascends bladder → proliferate and invade tissue • Bacterial toxins promote chemotaxis and activate granulocytes → free O2 radicals & lysosomal products released → tissue damage, fibrosis, scarring
Pathogenesis • interaction between bacteria and host 1. Bacteria - virulence factors 2. Host - perineal and urethral factors - bladder factors
• Virulence factors (vf) - virulence = ability of organism to cause disease - uropathogenic bacteria = strains selected from fecal flora because of specific vf that enhance colonization - adherence - K antigen - hemolysin etc
• Adherence - essential 1st step in UTI - bacteria attach to specific receptor sites on uroepithelium - mediated by fimbriae or pili - also by electrostatic and hydrophobic forces - able to ascend into upper UT in absence of structural abnormalities
• Fimbriae - P-fimbriae on E coli recognize & attach to specific receptor found within P blood gp Ag & uroepithelial cells - P-fimbriae = significant virulence factor (up to 94% pyelonephritic strains vs 23% cystitis strains) - S-fimbriae (7% uropathogenic strains) - marked binding ability with epithelial structures
• K antigen - capsular polysaccharide - shields bacteria from C’ lysis and phagocytosis • Haemolysin - cytotoxic protein - destroys uroepithelium, facilitating bacterial invasion - mice - produces more severe pyelonephritis
Escherichia coli
• Host defence • a) Perineal and urethral factors - short urethra in girls - perineal colonization from faecal flora - colonization of prepuce in boys
• b) Bladder factors - dysfunctional voiding - incomplete emptying - constipation - secretory IgA produced locally - alters bacterial adherence etc
When to look for UTI? • urinary tract symptoms • non-specific ill-health • sick kids especially neonates (septic workup) • anorectal anomalies • UT obstruction • spina bifida
Clinical features • may be non-specific (esp. neonates) - irritability, prolonged jaundice, feeding difficulties, vomiting, temperature instability, lethargy, diarrhoea, sepsis • bigger children - fever, frequency, dysuria, diarrhoea, abdominal pain, incontinence, cloudy urine, haematuria (26%)
Clinical features 1. Atypical UTI – includes pts who - are seriously ill - have poor urine flow - have abdominal or bladder mass - have raised serum creatinine - are septicaemic - fail to respond to antibiotics in 48 hours
What to look for • History including bladder & bowel habits. • Clinical exam: - abd - faecal masses. - genitals – meatal stenosis, phimosis, labial fusion, lax anal sphincter tone.
What to look for - spine – sacral agenesis, occult spina bifida (hairy patch, sacral dimple or tract, abnormal gluteal fold, lipoma, bony irregularity). • BP
ALWAYS BE SUSPICIOUS!! urine culture if uncertain and do it properly
How to collect a urine specimen • age-dependent • neonates / non-toilet-trained - suprapubic aspiration or catheter sample • toilet-trained child - clean-catch, mid-stream specimen • urine bag - easily contaminated (70%) • urine collection pad
Suprapubic Aspiration
Investigations • to confirm UTI • to look for UT abnormalities • range of Ix depends on - age of patient - availability of resources
1. Urine a) FEME - albumin, pus cells (WBC), RBCs - bacteria - gram stain b) culture & sensitivities * ensure correct collection method * send to lab ASAP
Investigations • Urine C&S - can be kept at 40C if not possible to send ASAP
Urine microscopy: UTI bacteriuria and pyuria
2. Blood a) FBC b) renal function - urea, electrolytes, creatinine c) others as necessary eg blood culture
Imaging Studies • Needs to be considered in certain categories of children ie - infants - atypical and recurrent UTI NICE clinical guidelines 54: UTI in children: diagnosis, treatment and long-term management. Aug 2007
3. Imaging a) Ultrasound scan - presence/absence of kidneys, dilatation/duplication of tract, calculi - operator-dependent - no ionizing radiation - in all children < 3 yrs old - in atypical UTI
Ultrasound scan: Kidneys
b) Micturating cystourethrogram (MCU) / VCUG - vesicoureteric reflux posterior urethral valves bladder trabeculation, diverticula - risk of radiation - needs urethral catheterisation - in recurrent UTI - in atypical UTI
MCU: VUR
c) Radionuclide scan DMSA (dimercaptosuccinic acid) scan - renal scars - differential function - in atypical and recurrent UTI
DMSA scan normal scar L upper pole
Management 1. General - fluid status - temperature control 2. Specific - antibiotics 3. Prophylaxis - controversial
General measures • not constipated • liberal fluids & regular, complete voiding / double-voiding • toilet hygiene - wipe from front to back • PROMPT recognition & TREATMENT of any breakthrough UTI
Constipation & its sequelae in UTI
Specific treatment • Antibiotics - iv if unwell, neonates - duration - at least 7 days - empiric – cephalosporins - reassess patient, urine culture & sensitivities
• Prophylactic antibiotics - should not be routinely prescribed - high urinary concentration eg trimethoprim, nitrofurantoin, cephalexin - may be considered in high grade VUR or recurrent UTI • More important to eliminate factors a/w recurrent UTI
VESICO-URETERIC REFLUX (VUR)
VUR • Def: reflux of urine into the ureter (and collecting system) • in 30 - 40% of children with UTI; 1 - 2% screened asymptomatic children • commonest radiological abnormality in children with UTI • thought to predispose to recurrent UTI and potential for scars
• Primary VUR = congenital anomaly of VU junction ie lateral displacement of ureteric orifice and shortened intramural course • inheritance – AD • Secondary - to - bladder outlet obstruction eg PUV - neurogenic bladder - surgery near / at vesico-ureteric junction
• Associated with - duplication anomalies of UT eg duplex system - renal dysplasia, MCDK - syndromes eg Eagle-Barrett • Reflux nephropathy = renal scarring a/w VUR • related to IRR - causes scars by its hydrodynamic effects + UTI
Eagle Barrett or Prune-belly syndrome
Classification: VUR • based on appearance of ureters and calyces during MCU • International Reflux Grading (1981): - I = ureter only - II = ureter, pelvis and calyces; no dilatation of tract, normal calyceal fornices
International Reflux Grading • III = mild / mod dilatation + tortuosity of ureter; mild/mod dilatation of pelvis; min blunting of fornices • IV = mod dilatation + tortuosity of ureter; mod dilatation of pelvis & calyces; complete blunting of fornices • V = gross dilatation & tortuosity of ureter; gross dilatation of pelvis; papillary impressions lost
IRS grading: VUR
Outcome • Primary VUR • 2 - 5 years F/U, resolution rate - 0 - 30% grade V - 50% grade III - 80 - 100% grades I - II
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