1. Uti in children

2. Introduction
Pediatric UTIs often signal an underlying genitourinary tract abnormality
Can lead to renal scarring with resultant hypertension and renal failure
Difficult to diagnose because symptoms are non-specific in this age group and testing is often invasive

3. Pediatric UTIs: Epidemiology
Prevalence
Girls—6.5-8%
Boys—2-3%
Uncircumcised boys have a 5-20 X increase in UTIs vs circumcised boys
Occurs in about 7% of children <2 who present with fever without a source

4. Epidemiology (continued)
Incidence of vesicoureteral reflux (VUR) is 1% in children < 2 yoa.
50% of kids <1 yoa with UTI have VUR
Early renal scarring is nearly twice as common in this age group.
Incidence of scarring increases with each subsequent UTI
Scarring occurs in 5-38% of febrile UTI’s.

5. Figure 1 Prevalence of VUR by age
Figure 1 Prevalence of VUR by age. Plotted are the prevalences reported in 54 studies of urinary tract infections in children (references in Technical Report).
Pediatrics 1999; 103:

6. Figure 2 Relationship between renal scarring and number of urinary tract infections.16
Pediatrics 1999; 103:

7. UTI: Classiffication Classification: Upper tract infection
Acute pyelonephritis- fever, bacteriuria, systemic symptoms
Lower tract infection
Urethritis
Cystitis
Voiding symptoms, little or no fever, no systemic symptoms

8. Clinical Presentation
Age and gender dependent
0 - 2 months:
Fever
2 mo.– 2 y/o:
Fever (>38 C)
Irritability
Vomiting and Diarrhea
Decrease appetite
Between 1-2 y/o = crying on urination, foul smelling odor
Females of all ages are more predisposed to UTI due to short urethra.Male urethra as an infant is also short.
What is the rationale for why a febrile UTI is pyelo until proven otherwise?The kidney is a complex organ as opposed to the bladder as a hollow viscus. Inflammation of the parenchyma of the kidney is responsible for fever.

9. Clinical Presentation
2 y/o – 6 y/o:
Systemic symptoms
Fever
Flank or back pain
Urgency, urinary incontinence, dysuria
Suprapubic or abdominal pain
Foul smelling odor
> 6 y/o and adolescents:
Same as above

10. Urethritis In female infants In adolescent girls and boys
Part of a diaper dermatitis
In adolescent girls and boys
Presenting sign of STD
In pre-school and school age girls
Part of “non-specific” vulvovaginitis
Generally environmental
Bubble bath
Nylon panties (also biker shorts, leotards, bathing suits)
Poor hygiene (not wiping, wiping back to front)
Overzealous hygiene
Use of baby powder, perfumes

11. Symptoms of urethritis
Dysuria
Reluctance to void
Perineal discomfort, erythema
May be associated with vaginal irritation and erythema in girls
In older boys, urethral discharge
In adolescent girls associated with PID symptoms
Symptoms are difficult to elicit in younger children secondary to lack of vocabulary

12. Cystitis Afebrile usually Frequency Enuresis Dysuria
Reluctance to void

13. Pyelonephritis
Usually associated with fever and systemic signs 2° renal parenchymal inflammation
Older children
Flank pain or abdominal pain
Younger children
Fever, irritability, vomiting, poor feeding

14. Pyelonephritis - Significance
EACH infection results in scar formation and reduced renal function
After diabetes mellitus and collagen vascular disease, undetected renal disease and untreated childhood UTI may be responsible for:
A large of portion of ESRD in adults
A huge need for dialysis and transplantation
It has been the assumption that renal scars are the RESULT of infection; could it also be that kidneys which are scarred or dysfunctional are at higher risk for infection? Is it an association or causality?

15. Pyelonephritis - Significance
Untreated childhood UTI responsible for:
Hypertension
Impaired kidney function
Complications of pregnancy

16. Causes and course of UTI

17. Risk Factors Age <1 year Female gender Uncircumcised males
Constipation
Voiding dysfunction
Improper wiping
Genitourinary abnormalities
Vesicoureteral reflux
Obstruction
Colonization with virulent E. Coli

18. Signs and Symptoms – Children 2 months to 2 years
Fever—usually unexplained
Vomiting and/or diarrhea
Abdominal Pain
Failure to thrive
Malodorous urine
Crying on urination

19. Signs and Symptoms – Children >2
Fever
Vomiting and/or diarrhea
Abdominal pain
Malodorous urine
Frequency and/or urgency
Dysuria
New incontinence

20. Summary
Urinary tract infections are a common cause of fever without a source in children <2 and can lead to renal scarring, HTN or ESRD. Rapid treatment is essential.
Symptoms are non-specific and thus a high level of suspicion is required
Urine culture is required for diagnosis, and should be obtained by catheterization or SPA when child is ill or infection is suspected
Treatment requires a 7-14d course of antibiotics
Prophylactic abx are required after initial treatment
All Children <2 require 2 imaging studies after initial UTI

21. References
Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999; 103:
Layton, KL. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinics in Family Practice 2003; 5: 2
Chon DH, Frank CL, Shortliffe LM. Pediatric Urinary Tract Infections. Pediatric Clinics of North America 2001; 48:
Linderd KA, Shortliffe LM. Evaluation and management of pediatric urinary tract infections. Urologic Clinics of North America 1999; 26:
McCollough M, Sharieff G. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed.2002;
Acute Urinary Tract Infections Clinical Effective Committee. Evidence based clinical practice guideline for patients 6 years of age or less with a first time acute urinary tract infection. Cincinnati (OH): Children’s Hospital Medical Center 1999; 1-14

22. Patient groups Options Time horizon NHS perspective
long-term antibiotic treatment for preventing recurrent urinary tract infections (UTI) in children
Patient groups
Infants of 1 year
Girls and boys
Recurrent UTI (no abnormalities)
Mild VUR (grade I and II)
Options
Long-term low dose antibiotics (Cochrane review)
(Trimethoprim, Nitrofurantoin, Cotrimoxazole)
Intermittent treatment of UTIs
Time horizon
3 years of long-term antibiotics and follow-up to end stage renal disease
NHS perspective

23. Model Structure for UTI

24. The evidence Effectiveness Existing reviews (variable quality)
Meta analysis, Multiple parameter synthesis
Probabilistic trial based model
Natural history
Epidemiological studies
Pooled trial baselines
Registry studies
Clinical judgement
Quality of life
Published studies
Survey
Costs
Published unit costs and dosage (BNF, PSSRU, CIPFA)

25. Antenatal Period The most common cause is physiologic dilation.
Metanephric urine production begins at 8 weeks, even before ureteral canalization is complete.
Transient obstruction with hydronephrosis occurs.

26. Embryology

29. Pathophysiology:
Anatomic and functional processes interrupts the flow of urine.
There is a rise in ureteral pressure causing stretching and dilation; if pressures continue to rise, leads to decline in renal blood flow and GFR.
When significant obstruction is persistent, it affects nephrogenic tissue and results in varying degrees of cystic dysplasia and renal impairment.

30. Grading of Severity of Hydronephrosis

31. Most Common Causes in Neonates:
Ureteropelvic Junction Obstruction
Ureterovesical Junction Obstruction
Posterior Urethral Valves
Eagle-Barrett Syndrome (a.k.a. Prune Belly Syndrome)
Vesicoureteral Reflux
Ureterocele

32. Treatment for UPJ: Pyeloplasty

33. Diagnosis

34. Urine Collection
Clean Catch acceptable for toilet trained children (wearing underwear or pull-ups)
Ensure cleansing with antiseptic towelette
Catheterized specimen in diapered children
Suprapubic bladder tap in <6 month old child is guaranteed sterile
Frequently, the nursing staff will need to give explicit instructions to parent or patient or actually assist in urine collection

35. Leukocyte Esterase Has to accumulate in urine
Insufficient accumulation possible in small infants who void frequently
Infants <3 months old may not have mature enough immune system to induce leukocytes in urine (beware neutropenia on CBC)

36. Nitrites
By-products of E. coli and other lactose fermenters (glucose digestion)
Insufficient accumulation possible in small infants who void frequently
Insufficient accumulation possible in older child during the day and in older patient who has significant frequency
If positive, highly suggestive of UTI (high specificity)

37. Microscopy >10 WBC/hpf on spun urine
Bacteria on unspun urine are common unless catheterized specimen
Gram stain is very helpful on spun urine
Standard UA plus gram stain is “enhanced UA”
Usually reported as “5-20” or “<5”…so what to do if you are looking for >10??

38. Urine Culture >100,000 cfu per mL on any culture
>10,000 cfu per mL on cath specimen
ANY bacterial growth on bladder tap (at least 1,000 cfu/mL)

39. Sensitivity and Specificity of
Components of the UA
Sensitivity %
(Range)
Specificity %
(Range)
Test
Leukocyte esterase
Nitrite
Leukocyte esterase or nitrite positive
Microscopy: white blood cells
Microscopy: bacteria
Leukocyte esterase or nitrite or
Microscopy positive
83 (67.94)
53 (15-82)
93 (90-100)
73 (32-100)
81 (16-99)
99.8 (99.100)
78 (64-92)
98 (90-100)
72 (58-91)
81 (45-98)
83 (11-100)
70 (60-92)

40. Urine Cultures Held for 48 h but usually positive at 24 h for true UTI
Requires another day for ID of organism
May require another day for sensitivities
If contains skin flora (S. epi., S. aureus or α-strep.) considered contamination secondary to poor specimen collection

41. Diagnosis
Urinalysis
Can be obtained by most convenient means if infant is not ill
UTI CANNOT be diagnosed with UA alone
If suspicious UA, the Urine Culture must be obtained via SPA or catheter specimen
If UA does not suggest UTI, it is reasonable to follow child clinically

42. Sensitivity % (Range) Specificity % (Range)
Table 1. Sensitivity and Specificity of Components of the Urinalysis, Alone and in Combination (References in Text)
Test
Sensitivity % (Range)
Specificity % (Range)
Leukocyte esterase
83 (67-94)
78 (64-92)
Nitrite
53 (15-82)
98 (90-100)
Leukocyte esterase or nitrite   positive
93 (90-100)
72 (58-91)
Microscopy: WBCs
73 (32-100)
81 (45-98)
Microscopy: bacteria
81 (16-99)
83 (11-100)
Leukocyte esterase or nitrite or   microscopy positive
99.8 (99-100)
70 (60-92)
Pediatrics 1999; 103:

43. Diagnosis Urine Culture MUST be collected via catheter or SPA
UTI CANNOT be diagnosed from a bag specimen
Diagnosis of UTI requires Urine Culture
LOE--Strong

44. Urine Collection: Suprapubic Aspirate
“Gold standard” - >99% specificity
Positive culture: any number of g- bacilli or >3000 CFU of g+ cocci

45. Urine Collection: Transuretheral Catherization
>105 CFU - 95% specificity
104 – 105 CFU – infection is likely
103 – 104 CFU – Suspicious
<103 CFU – infection unlikely

46. treatment

47. Treatment May initiate treatment either orally or parenterally
Admit and use parenteral antibiotics if toxic, dehydrated or unable to take PO
Choices:
TMP/SMX
Cephalosporin
Amoxicillin (check local resistance)

48. Treatment--continued
Improvement should be seen in hours
If not having expected clinical response in 2 days, re-culture, consider changing antibiotics and do imaging studies
Complete 7-14 day course of antibiotics
14 days should be given for those that were ill with clinical evidence of pyelonephritis

49. Prophylaxis
After completion of initial antibiotics, children should be give a prophylactic dose of antibiotics until imaging studies complete
Antibiotic should have high urinary excretion and low serum and fecal levels, thus minimizing the development of resistance.

50. Imaging
Needs to be performed in ALL children <2 years old with initial UTI
Need to perform at least 2 studies to image the upper and lower urinary tracts
Acute imaging only necessary when appropriate clinical response is not achieved within 2 days

51. Ultrasound
Should be done on all infants < 2yoa after their initial UTI
Helps to detect hydronephrosis and ureteral dilation
Has replaced IVP
Need additional study to evalute VUR
Is not as sensitive as renal cortical scintigraphy (DMSA) for detecting inflamation and scarring

52. Voiding Cystourethrography (VCUG)
Used to identify and grade reflux
Also evaluates the urethra and bladder for abnormalities – important for boys who may have posterior urethral valves and girls with voiding dysfunction
Radionuclide cystography (RNC) – can also evaluate reflux, but does not delineate the lower tract anatomy well. Can be used for follow-up exams as has low ratiation dose

53. Renal Cortical Scintigraphy (DMSA)
Very sensitive for evaluating acute inflammation from pyelonephritis as well as renal scarring
Role in clinical management is still unclear

54. Treatment No “short course” therapy for small children
No “short course” therapy for males
Empiric therapy is directed at organisms and adjusted for age.
Choose narrowest spectrum allowable considering host factors
Adjust therapy when sensitivities available
Short course is NOT indicated for pyelonephritis but a recent study suggests it is acceptable in cystitis in children
Arch Dis Childhood 2002 August 87 (2) :

55. IV antibiotics-Indications
Any person of any age who appears clinically toxic or who has neutropenia
Infants <1 mo until bacteremia, sepsis, & meningitis ruled out
Children unable to tolerate oral antibiotics
Immunocompromised patients
Multiple studies show NO benefit to outcome for children treated parentarelly vs orally.
Arch Pediatr Adol Medicine 2001 Feb 155(2), “The addition of ceftriaxone to oral threapy does not improve outcome in febrile children with urinary tract infections.
J Chemother, 2001, June:13(3): Comparative study of cefixime alone vs. intramuscular ceftizoime followed by cefixime in the treament of urinary tract infections in children

56. Antibiotic choice Neonates
Ampicillin plus a second antibiotic (usually gentamycin or cefotaxime) to cover for GBS, Listeria, as well as gram negative organisms
S. aureus and S. epi. can cause hematogenous pyelonephritis (in children instrumented :ET tube,central lines, etc)
Vancomycin may be indicated for toxic patients or those unresponsive to initial therapy

57. Therapy
Cefixime (Suprax) oral is as effective as parenteral ceftriaxone
Cefpodoxime (Vantin)
Bad tasting
10 mg/kg/day
Fluoroquinolones are expensive and ”off label” in pedi
Rationale is to cover for fecal coliforms which are usual culprits Need to be cognizant of local organisms; there is literature that supports the idea that Bactrim may be facing increasing levels of resistance in UTI organisms; fluoroquinolones may soon be approved for children less than 12 but are more expensive than most cephalosportins
J Chemother Jun;13(3):
Related Articles, Links
Comparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children. Gok F, Duzova A, Baskin E, Ozen S, Besbas N, B

58. Bacterial virulence Bacterial spectrum at the Ist Dept
Bacterial virulence Bacterial spectrum at the Ist Dept. of Pediatrics, in
N= (%)
E. coli
Enterococcus faecalis 13
Proteus indol neg. 10
Klebsiella
Pseudomonas spp 7
Enterobacter spp 6
Proteus indol pos 3
Staphylococcus
Other

59. Sensitive host Age related factors
Anatomy (short urethra, phymosis and adhesio cellularis preputii et labia minora, diaper)
colonization
Immunological susceptibility
Mucosal barrier
Inherited/acquired
immunresponse
Ex: IgA deficiency, P1 blood group

60. Sensitive host Anatomical malformations obstruction VUR
meningomyelokele
prune-belly syndrome
Stone disease, etc

61. Age-related incidence of UTI

62. Management of UTI

63. Prognosis

64. UTI Controversy #1: Antibiotic Prophylaxis
Indications
 grade 1 VUR
frequent UTI recurrences
Problems
Pt Rxd with antibiotic prophylaxis
Increased infection with Proteus and Enterobacter
pseudomonas and Candida increased in children with urogenital abnormalities
Drug toxicity and sensitivities
Antimicrobial choices (qhs better)
TMP-SMX or Nitrofurantoin (GI disturbance)
Keflex if < 3 months
Quinolones in some circumstances

65. Posterior Urethral Valves
Abnormal congenital mucosal folds that are thin membranes impeding bladder drainage.
Most common obstructive urethral lesion in male newborns found at the distal prostatic urethra.
Incidence is approx’ly 1 in 8,000 males.
Approx’ly 50% have reflux.
VCUG is the modality of choice.

66. Radiographic signs of PUV:
distended prostatic urethra
valve leaflets
bladder and/or bladder neck hypertrophy
diverticula
narrow stream in the penile urethra
incomplete emptying of the bladder

67. Treatment of PUV:
Transurethral valve ablation, vesicostomy or upper tract diversion
Urethral stricture is a common complication
Fetal intervention carries a high risk with mortality rate of 43%
ESRD, renal insufficiency and chronic renal failure are long-term consequences

68. 30% of boys with posterior urethral valves whose symptoms present in infancy are at risk for progressive renal insufficiency.

70. PUV, 2 months , MCU

71. PUV, 2months

72. Mcu done for suspected PUV

73. 9 months old child with dribbling of urine and difficulty in passing urine
?PUV
MCU done
Uroprophylaxis suggested
Told by another Doc: not necessary
Came with high grade fever after 1 month
UTI

75. Vesicoureteral Reflux
Retrograde propulsion of urine into the upper urinary tract during bladder contraction.
Primary reflux is caused by attenuation of the trigone and the contiguous intravesical ureteral musculature.
May be caused by the ectopic insertion of the ureter into the bladder wall resulting in a shorter intravesicular ureter, which acts as an incompetent valve during urination.

76. The ratio of the submucosal tunnel length to the ureteral diameter is the primary factor determining the effectiveness of the normal valve mechanism.
It is normally 5:1, and in those with reflux it is 1.4:1.
The intramural length increases from 0.5 cm at birth to 1.3 cm by 12 years of age.
Duplication of the collecting system and ureteroceles should also be considered.

78. Some clinical facts about VUR:
It is genetic.
Occurs in about 30% of first-degree relatives.
1/3 of children with a urinary tract infection has reflux on VCUG.
Primary reflux tends to resolve over time as intravesical segment elongates with growth.

79. Grading of Vesicoureteral Reflux

80. VUR Grading Prognosis - 5% adults Scarring - 5-50% Screening UTI
Grade I
Grade II
Grade III
Prognosis - 5% adults
Scarring %
Screening
UTI
Grade IV
Grade V

81. Prognosis: Resolves spontaneously before adolescence in:
Kidney is most susceptible to scarring in the first year of life and at the time of first upper tract infection.
Scars less frequently develop after the age of 5.
VUR and scarring lead to hypertension, progressive renal insufficiency and failure.
Resolves spontaneously before adolescence in:
90% of Gr. 1 reflux
80% of Gr. 2
50% of Gr. 3
10% of Gr. 4
0 in Grade 5 reflux

82. Treatment: Observation Medical treatment of infections
Surgical treatment
significant hydroureteronephrosis
indicated if impossible to keep urine sterile and reflux persists
acute pyelonephritis occurs
evidence of increasing renal damage

83. VUR

84. MCU
C/o Recurrent UTI

86. Endoscopic submucosal injection

87. Endoscopic submucosal injection
Teflon
Silicon
Collagen

88. Bacterial virulence
Virulence=factors that enable bacteria to invade the urinary tract
Surface antigenes
O: lipopolysacharides with endotoxin properties. Induces fever, local inflammation
K, (capsular) antigene, prevents phagocytosis
“P” fimbriae: bind to glycolipid receptors of the P blood group family
A number of further factors not routinely checked

89. Bacterial virulence Pyelonephritis: 3-4 (known) virulence factors
Cystitis: 0-2 factors
CAVE: OBSTURCTION !! MALFORMATION !!