Urinary tract infection in children

1. URINARY TRACT
INFECTION IN CHILDREN
DR. RISHABH SINGH (PG)
DR. PRAVEEN (SR)
DR. DEEPAK SACHAN (MODERATOR)

2. INTRODUCTION
• Invasion of urinary tract by pathogens, which may involve the
upper or lower tract
• An acute illness usually accompanied by fever, with or without
other constitutional symptoms, and local symptoms of loin pain
and bladder irritation.
• Causes significant morbidity.
• The importance of UTI rests in the acute illness it causes and the
risk of recurrence

3. EPIDEMIOLOGY
• Most common in children less than 1 year
• Prevalence of afebrile symptomatic UTIs in children over 1
year is 8%
• Prevalence in febrile infants is 7%.
• Rapid evaluation and treatment of UTI is important to prevent
renal parenchymal damage (renal scarring) that can cause
hypertension and chronic renal failure later.

4. EPIDEMIOLOGY
Male : Female
variation
Infancy
M:F::2.8:5.4
20% in febrile
uncircumscribed
males
>1 yr
M:F::1:10
•In females the first UTI usually
occurs by the age of 5 yr
•Obstructive lesions may be found in 5-
10 % of boys investigated for UTIs and
30 % patients show VUR
•Increased risk in malnourished and
chronic diarrhoea patients
•Diagnosis often clinically missed –
non specific symptoms

5. ETIOLOGY
• Primarily caused by colonic bacteria - Escherichia coli (E. coli) causes 54-67%
UTIs, followed by Klebsiella , proteus , Enterococcus and pseudomonas.
• Proteus species are common causes of UTI in uncircumcised boys and cases of
urolithiasis.
• Staphylococcus saprophyticus causes acute UTI in adolescent girls.
• Other organisms including Staphylococcus epidermidis and Streptococcus faecalis
may occasionally be responsible.

6. • Proteus and Pseudomonas are associated with recurrent UTI,
instrumentation and nosocomial infections.
• Adenovirus should be suspected in acute hemorrhagic cystitis.
• Pathogens of low virulence and fungi may be causative in patients who
are immunocompromised.
• Candida albicans infections are relatively common in preterm
infants, immunocompromised children and following prolonged
antibiotic therapy.

7. Risk factors
• Female gender
• Uncircumcised male
• Vesicoureteral reflux*
• Toilet training
• Voiding dysfunction
• Obstructive uropathy
• Urethral instrumentation
• Wiping from back to front in
girls
• Tight clothing (underwear)
• Pinworm infestation
• Constipation
• Bacteria with P fimbriae
• Anatomic abnormality (labial
adhesion)
• Neuropathic bladder
• Sexual activity

8. PATHOGENESIS
• In healthy young children the periurethral area contains bowel bacteria –
predominantly E. coli in girls and, after the first 6 months of life, Proteus in boys.
• Studies have shown that colonization with gram-negative bacteria precedes the
development of UTI - may be induced by a course of a broad spectrum antibiotic for
another infection
• The development and severity of a UTI depend on bacterial virulence factors and on
the innate host immune system. Uropathogenic bacteria spread to the periurethral
area ascend the urinary tract against urine flow establish infection.

9. HOST RESPONSE TO UTI
• Host resistance to UTI depends on host innate immunity. The response to E. coli is
activated by P fimbriae mediated adhesion to glycolipid receptors leading to activation of
Toll-like receptors (TLR)
• TLR4 signalling leads to the release of transcription factors – Interferon Regulatory Factor
IRF3 - triggering cytokine production and neutrophil recruitment to kill bacteria.
• Uroepithelial cells secrete IL-6, activates CRP production, and stimulates the production of
mucosal IgA. Infected cells also produce IL-8 ,which increases neutrophil migration and
activation resulting in pyuria.

10. • In children with acute pyelonephritis, a specific immune response
develops after 3–7 days.

11. Genetic variations:
• Children with asymptomatic bacteriuria express lower levels of TLR4 . Low TLR4
expression results from mutations in the TLR4 promoter.
• Single nucleotide polymorphisms (SNP) in the IRF3 promoter have been identified in
about 80 % of patients with recurrent episodes of acute pyelonephritis.
• Also reduced expression of the IL-8 receptor, CXCR1, associated with SNPs in the
CXCR1 gene, is found in children with frequent episodes of acute pyelonephritis.
• Individuals of blood group P lack functional receptors for P fimbriae, while children with
blood group P1 have an increased risk of acute pyelonephritis.

12. CLASSIFICATION
According to the site of infection
Upper Urinary Tract Infection
• Acute pyelonephritis: Inflammation of renal pelvis and parenchyma with symptoms-
Fever with /without abdominal pain, loin pain, nausea, vomiting & occasionally
diarrhoea. Fever > 39 ° C without another source lasting >24 hours in males and >
48hrs in females.
Lower Urinary Tract Infection
• Acute cystitis: Inflammation of Bladder mucosa with Lower urinary tract symptoms
(dysuria, urgency, new-onset urge incontinence, frequency, suprapubic pain) ,
possibly malodorous urine with no fever or low-grade fever (<38 C) together with a
significant growth of bacteria on urine culture.

13. According to symptoms:
Asymptomatic or covert bacteriuria:
• Defined as bacteria in urine on microscopy and gram stain in an afebrile asymptomatic
patient with pyuria.
• The causative organisms, mostly E.coli, are of low virulence and proposed to prevent
colonization by virulent strains.
Symptomatic UTI :
• Irritative voiding symptoms, suprapubic pain (cystitis), fever, and malaise (pyelonephritis).

14. According to severity:
Complicated UTI:
• Fever > 39°C with marked toxicity, persistent vomiting, dehydration and renal angle
tenderness
Uncomplicated UTI:
• Occurs in patients who have a normal, unobstructed genitourinary tract, who have no
history of recent instrumentation not with marked toxicity.

15. RECURRENT URINARY TRACT INFECTIONS
• Defined as the recurrence of symptoms with significant bacteriuria in patients
who have recovered clinically following treatment
• Children, usually girls in the school age group, with an anatomically and
functionally normal urinary tract may develop recurrent lower tract afebrile UTI.
• Proteus and pseudomonas are seen to cause recurrent UTIs
• The risk Factors include VUR, PUV obstruction, Spinal cord defects, &
neurogenic bladder.
• Many of these children may have symptoms of bladder instability, such as urge
incontinence or squatting.
• Recurrent UTI add to parental anxiety, medical costs and the risk of renal
parenchymal damage in young infants.
Definition- Management of UTI ; Indian Society of Pediatric Nephrology

16. TERMS USED
Significant bacteriuria Colony count of > 105 / ML of a single species in a midstream
clean catch sample.
Asymptomatic bacteriuria Significant bacteriuria in the absence of symptoms of urinary tract
infection (UTI).
Simple UTI UTI with low grade fever, dysuria, frequency, and urgency; and
absence of symptoms of complicated UTI.
Complicated UTI Presence of fever >39ºC, systemic toxicity, persistent vomiting,
dehydration, renal angle tenderness and raised creatinine.
Recurrent infection Second episode of UTI.

17. SYMPTOMS
Neonates and Infants
• Nonspecific symptoms including FTT, vomiting, diarrhoea. Urine may be foul
smelling.
• Acute pyelonephritis presents with features of sepsis such as lethargy,
seizures, shock, unstable temperature and persistence of physiological
jaundice.
• Below two years of age having unexplained fever.
• Infants and young children are at higher risk for acute renal injury from UTI.

18. Older Children
• Dribbling, prolonged voiding, straining, crying during micturition and poor urinary
stream indicate an abnormality of the distal urinary tract.
• Diurnal incontinence, urgency, frequency and squatting suggest voiding dysfunction.
Dysuria, frequent voiding and hypogastric pain suggest cystitis.
• Fever, chills and rigors and flank pain indicate renal parenchymal involvement.
• Gross haematuria occasionally.
• The presence of fever is regarded as indicative of pyelonephritis.
Patients with urinary stasis (mechanical or neurogenic) having UTI from urea
splitting organisms, usually Proteus but also Klebsiella, are at risk of developing
hyperammonaemia and encephalopathy.

19. HISTORY
• Obtain voiding history (stool, urine) stream characteristics in toilet trained
children
• Circumcision, sexual abuse, parasitic infections like pin worm
• Recent antibiotic use & family history of VUR
• Recurrent UTIs or CKD
• Evaluation of growth curve

20. Features of Underlying Structural Abnormality
• Distended bladder /Palpable, enlarged kidneys
• Tight phimosis; vulvar synechiae
• Patulous anus; neurological deficit in lower limbs
• Urinary incontinence
• Previous surgery of the urinary tract, anorectal malformation or
meningomyelocele

21. Features of Bowel Bladder Dysfunction
• Recurrent urinary tract infections
• Persistent high grade vesico-ureteric reflux
• Constipation, impacted stools
• Maneuvers to postpone voiding (holding maneuvers, e.g. squatting)
• Voiding less than 3 or more than 8 times a day
• Straining or poor urinary stream
• Thickened bladder wall >2 mm
• Post void residue >20 mL

22. INVESTIGATION
• Complete blood count-neutrophilic leukocytosis
• Serum urea ,creatinine ,electrolytes
• ESR > 30mm in 1st hr
• CRP> 20mg/dl (non specific)
• Serum procalcitonin > 0.5 ng/ml
• Urine analysis -biochemical test and microscopy
• Urine culture and sensitivity
• Blood culture should be done in infants and children with complicated UTI

23. Nitrite test:
Purpose:
• Used to detect nitrites produced by reduction of dietary nitrates by urinary
gram negative bacteria (especially E. coli, Klebsiella and proteus)
Findings:
• Positive test is strongly suggestive of UTI because of high specificity. Nitrite
sensitivity is 15-82% and specificity is 90-100%
Special circumstances:
• False negative (low sensitive) results commonly occur with insufficient time for
conversion of urinary nitrates to nitrites (age dependent voiding frequency) and
lack of ability of bacteria to reduce nitrates to nitrites (many gram positive
organisms such as enterococcus , mycobacterium spp. and fungi).

24. Leucocyte esterase test:
Purpose:
• Used to detect esterases released from broken down leukocytes. An
indirect test for WBCs
Findings:
• Positive test is more sensitive(67-84%) than specific(64-92%) for a UTI

25. COLLECTION OF URINE SAMPLES
NICE recommended techniques
A ‘clean- catch’ sample into a waiting sterile pot when the nappy is removed;
this is easier in boys.
In the older child, urine can be obtained by collecting a midstream sample as
in adults.
Careful cleaning and collection are necessary, as contamination with both
white blood cells (WBCs) and bacteria can occur from under the foreskin in
boys, and from reflux of urine into the vagina during voiding in girls.

26. Toilet Trained children

27. Suprapubic aspiration (SPA)
• Method of choice in the severely ill infant under 1 year requiring urgent
diagnosis and treatment, and in cases where previous samples have
suggested contamination.
• NICE guidelines recommend this be performed when non- invasive
methods are not possible.
• It is recommended that Ultrasound imaging should be performed to
confirm the presence of urine in the bladder and to guide SPA.

29. BAGGED SPECIMEN
• An adhesive plastic bag applied to the perineum after careful washing
• There may be contamination from the skin and the false positive rate is
85%.
• Method should only be used as a screening test.
• A negative result confidently excludes a diagnosis of UTI.

30. CATHETER SPECIMEN
• Do not disconnect the closed drainage system as infection may be
introduced ,or take the sample from the urinary drainage bag as the specimen
may be contaminated.
• Perform hand hygiene and put on gloves, using an aseptic non-touch
technique, clean the catheter sampling site .
• This is collected from the self-sealing bung of the urinary drainage
tubing in a child who is already catheterised.

32. DIAGNOSIS
• UTI may be suspected based on symptoms or findings on urine analysis
or both , a urine culture is necessary for confirmation and appropriate
therapy.
• Nitrite test
• Leukocyte esterase test
• Pyuria : >/= 5 WBCs/hpf
• Absence of pyuria is rare if UTI is present

33. Urine culture
• Suprapubic aspiration : > 50,000 colony forming units (CFUs). Some resources do
consider <50,000 CFUs diagnostic of a UTI. Recommended clinical correlation
• Transurethral catheterization : > 50,000 CFUs
• Clean Catch > 105CFUs
• Bagged specimen : positive culture can not be used to document UTI
• Catheter associated ( indwelling urethral or suprapubic ): No specific data for
pediatric patients.
Adult Infectious Diseases Society of America Guidelines define it as presence of
symptoms and signs compatible with UTI and > 1000 CFU /ml of one or more bacterial
species in a single catheter urine specimen or in a midstream voided urine specimen
from a patient whose catheter has been removed within 48 hours.

34. Sensitivity and Specificity of Urinalysis

35. Newer Markers
• Urinary N-acetyl-b-glucosaminidase
• Marker of tubular damage, Increased in febrile UTI
• Possible reliable diagnostic marker for UTIs, also elevated in VUR
• IL-6
• Clinical use of urinary concentrations of IL-6 in UTIs ,still at research stage
S Raimund ,D Hasan S, H Piet Hoebeke Urinary Tract Infections in Children: EAU/ESPU Guidelines2014 European
Association of Urology 2014:67:546
Jantausch BA, et al. Urinary N-acetyl-beta-glucosaminidase and beta-2-microglobulin in the diagnosis of urinary tract
infection in febrile infants. Pediatr Infect Dis J, 1994. 13

36. Imaging techniques
Ultrasonography
• Provides information regarding kidney size and location,
hydronephrosis, urinary bladder anomaly, post void residual
volume
• Can be performed during therapy
• Limitation-operator dependence and poor sensitivity for
detection of VUR
MCU
• Conventional voiding cysto-urethrography (VCU)-Necessary
for diagnosing and grading of severity of VUR, Urethral and
bladder anomaly
• Radionuclide cystography (indirect)
• Cystosonography
Radionuclide
studies
• Sensitive for detection of renal scars
• Tc-99m DMSA shows a specificity of 100% and sensitivity of
80% for renal scarring.

37. VCUG in a child with a history of UTI. B/l
VUR with ureteral dilatation
Grading of VUR on micturating cystourethrogram. Grade I: Reflux
into the nondilated distal ureter;
grade II: Reflux into the upper collecting system in nondilated
ureter; grade III: Reflux into dilated ureter; grade IV: Reflux into
grossly dilated ureter; grade
V: Massive reflux with ureteral dilation and tortuosity and
effacement of calyceal details

39. <1 year 1-5 years
Further evaluation
-in first episode of UTI in Boys,
-not indicated in Girls

40. MANAGEMENT GOALS
• Elimination of symptoms and eradication of bacteriuria in the acute
episode
• Prevention of renal scarring
• Prevention of a recurrent UTI
• Correction of associated urological lesions

41. TREATMENT
Acute cystitis:
• If treatment started before the results of culture are known – cefixime at 8-10
mg/kg/day in two divided doses.
• Nitrofurantoin (5-7 mg/kg/24 hours in 2 divided doses) is effective against
Klebsiella and Enterobacter.
• 3 to 5 days course of therapy with trimethoprim-sulfamethoxazole (TMP-SMX)
(6-12 mg TMP/kg /day in 2 divided doses)

42. Uncomplicated UTI:
• To be treated for 7-10 days.
Acute febrile UTIs :
• where it is difficult to differentiate UTI and pyelonephritis , a course of antibiotics for 7-
14 days.
• Children who are dehydrated , are vomiting are unable to drink fluids have
complicated infection, or in whom urosepsis is a possibility should be admitted to
hospital for IV rehydration and IV antibiotics.
• Ceftriaxone (50 mg/kg/24 hrs, not to exceed 2 grams) or cefepime (100mg/kg/24hrs
q12h) or cefotaxime (100-150 mg/kg/24 hrs in 3-4 divided doses, until cultures are
back to determine narrow spectrum antibiotics .

43. • Oral 3rd generation cephalosporin such as cefixime is as effective
against gram negative organisms except P. aeruginosa, and so TOC
for outpatient therapy.
• FQs like ciprofloxacin OR aminoglycoside is an alternative for
resistant microorganisms especially P. aeruginosa. Levofloxacin is
an alternative with good safety profile in children.
• However, clinical treatment with FQs in children should be used with
caution because of potential cartilage damage.

44. Oral Antibiotics
Drug Dose(mg/kg/day) Remarks
Amoxicillin co-amoxiclav 30-50 in 2-3 divided doses Of choice for
uncomplicated UTI; risk of
resistance
Cephalexin 30-50 in 3 divided doses For uncomplicated UTI ;
not effective against
Proteus
Cefadroxil 30-40 in 2 divided doses
Cefixime 10 in 2 divided doses Broad spectrum agent
Ciprofloxacin 10-20 in 2 divided doses Avoid: <3 months, G6PD
deficiency;
lowers seizure threshold

45. Parenteral Treatment
Drug Dose(mg/kg/day) Remarks
Gentamicin 5-6 in 1-2 divided doses Once daily dosing effective
Amikacin 10-15 in 1-2 divided doses
Cefotaxime 100 in 2-3 divided doses Safe and convenient for
use as single medication
Ceftriaxone 75-100 in 1-2 divided
doses
Ampicillin 100 in 2-3 divided doses Combine with
aminoglycoside

46. Response to therapy
• Adequate therapy leads to resolution of toxicity within 24-48 hrs and fever by 48 -72
hrs
• Urine culture becomes sterile after 48 hrs of appropriate antibiotics
• Repeat urine culture not required during or following treatment unless symptoms fail to
resolve despite 72 hrs of adequate antibiotic therapy, symptoms recur, suggesting
recurrent UTI, contamination of initial culture is suspected
• Failure to respond may be due to presence of resistant pathogens, complicating
factors or noncompliance requiring re-evaluation

47. Long- term management
• Medical measures for the prevention of urinary tract infection
• High fluid intake to produce a high urine output.
• Regular voiding.
• Complete bladder emptying using double micturition to empty any
residual or refluxed urine returning to the bladder.
• Prevention or treatment of constipation.
• Good perineal hygiene.
• Lactobacillus acidophilus

48. Prophylaxis
Indication
• UTI below 1 year of age, while awaiting imaging studies
• VUR
• Frequent febrile UTI (3 or more episodes in a year) with normal
urinary tract

49. Prophylaxis
Drug Dose(mg/kg/day)* Remarks
Cotrimoxazole 1-2 ,of trimethoprim Ensure fluid intake; avoid in
infants <6 weeks-old, and G6PD
deficiency
Nitrofurantoin 1-2 GI upset common; avoid in G6PD
deficiency, infants <3 months,
renal insufficiency; bacterial
resistance rare
Cephalexin 10 Used in young infants where use
of NFT and cotrimoxazole is
restricted
Cefadroxil 3-5
Cefaclor 5-10
Cefixime 2

50. Potential treatment & prevention
• Probiotic therapy that replaces urogenital flora. These bacteria may
inhibit growth of other bacteria.
• Cranberry juice may prevent bacterial adhesion and biofilm formation,
hypothesized to be via proanthocyanidin
Insufficient data regarding these therapies to reduce UTIs.

51. References
• Nelson Textbook of pediatrics 21st edition
• The Harriet Lane Handbook 21st edition
• Pediatric Nephrology 7th Edition; Ellis D. Avner , William E.
Harmon,Patrick Niaudet, Norishige Yoshikawa,Francesco
Emma, Stuart L. Goldstein
• Paediatric Nephrology 3rd Edition; Lesley Rees
• Pediatric Nephrology 6th edition RN Srivastava , Arvind bagga

52. THANK YOU!