1. Urinary Tract Infection
Ali Derakhshan M.D. Shiraz University of Medical Sciences, Shiraz-Iran

2. Importance of UTI Of febrile neonates, up to 7% have UTIs.
The acute illness it causes and recurrence
UTI may cause renal scar which in turn cause HTN and CKD
Risk of ESKD with UTI without structural abnormality is negligible
Of febrile neonates, up to 7% have UTIs.
By the age of 7, 8.4%of girls and 1.7%of boys at least one UTI
More UTI in boys in the 1st 6months of life
Prevalence of UTI in febrile children<5yrs was 3.4% and in children0-24 months was 7%
High Prevalence in uncircumcised boys 20.1%vs 2.4%
Independent risk factors for recurrence age<5 and
VUR grade 3-5
Craig JC,et al. BMJ.2010;340:1594
Shaikh N,et al. Pediatr Infect Dis J. 2008;27

3. CASE 1 A 6 month old ♀ infant with 2days fever, feeding , past Hx including antenatal US: negative on P Exam: mild dehydration, temp:39c, otherwise normal except for severe labial adhesion UA: nit+, many WBC, leukocyte esterase+ Next step:

4. Appropriate U/C and empiric Antibiotic therapy waiting for UC result Estrogen conjugated cream *1-2 wk.

5. Case 1 Continued…. U/c Ecoli>105
Sensitive to: Cotrimaxozole, itrofurdantin, Nalidix…, Gent.., Amikacin, Cefixim*, efrtioxane,cipro…,
Resistant to: ampicillin
? ?
1st DOSE *2

6. Management of UTI Indications for admission Age<2-3mo,
septic, dehydrated, vomiting,
immunocompromized , single kidney, known gross anatomical abnormality or obstruction,
Recent treatment for UTI and recent instrumentation
Patients from far distances and non-compliant 6

7. Recommendations AAP Duration of treatment: 7–14 days
Choice of route: Initiating treatment orally or IV is equally efficacious, so choice is based on practical considerations.
Choice of drug: Based on local sensitivity patterns, adjusted according to sensitivity of particular uropathogen and general condition of the pt.
Duration of treatment: 7–14 days

8. Clean catch NOT acceptable
Making the Diagnosis
Most Important
Be Suspicious and test at risk children
Rule
Urine Culture!!
Suprapubic – MOST accurate, MOST invasive
Transurethral – Accurate, better tolerated
Clean catch – Acceptable if toilet-trained
Urinary bag – NOT acceptable for culture
Clean catch NOT acceptable if
being hospitalized
For IV treatment

9. COMMON MICROORGANISMS CAUSING UTI
Common (More Virulent)
Rare (Less Virulent)
E.Coli(80%)
pseudomonas
proteus
Group B strep
klebsiella
Staph (aureus, epidemidis)
Staph.saprophyticus
Haemophilus influenzae
Enterococcus
Enterobacter
Escherichia coli causes 75 to 90 percent of episodes of acute uncomplicated cystitis, and Staphylococcus saprophyticus accounts for 5 to 15 percent, mainly in younger women. Enterococci and aerobic gram-negative rods other
than E. coli,such as klebsiella species And Proteus mirabilis, are isolated in the remainder of the cases.
Common contaminants: lactobacillus sp…, corynebacterium sp, ά-hemolytic strep, Coagulase-negative staph

10. URINARY TRACT INFECTION
Acute pyelonephritis (Adult): systemic and local signs and symptoms of fever, chills, malaise, flank pain, back pain, and or flank tenderness
Acute pyelonephritis (children): fever(T≥38.5ºC±), diarrhea, vomiting, Poor feeding,…………….
Acute cystitis: dysuria, frequency, urgency, incontinence/enuresis, suprapubic pain or tenderness, T≤38ºC

11. ASYMPTOMATIC BACTERIURIA
 It refers to a condition that results in a positive urine culture without any manifestations of infection.
 It is most common in girls.
 The incidence is 1–2% in preschool and school-age
girls and 0.03% in boys. The incidence declines
with increasing age.

12. COMMON MISTAKES IN DIAGNOSIS OF UTI
Lower urinary symptoms not always UTI
Lower urinary symptoms (dysuria, frequency, urgency, itching ): vaginitis, vaginal FB, Uretheral FB, pinworms, local irritants (bubble baths) , hypercalciuria , sexual abuse, labial fusion, meatal stenosis, phemosis, balonitis,…..
WBC in Urine: Fever, dehydratin, hypercalciuria, stone, nephrocalcinosis, cystic kidneys, vaginitis, urethritis,………….

13. But… In Infants Fever! Fever!! Fever!!! Lack classic signs
Irritability
Poor feeding
Vomiting,diarrhea,jaundice

14. Recurrence, Reinfection, Relapse
Recurrent UTI:
2 or more episodes of acute pyelonephritis (upper UTI), or one episode upper UTI plus one or more episode cystitis or 3 or more episodes of lower urinary tract infection
Reinfection is a UTI that occurs more than 2 weeks after antibiotic treatment of the original UTI is completed; it may be caused by the same bacteria as the original infection or a different one.
Relapse is a UTI caused by the same bacteria as the original UTI that occurs within 2 weeks after the individual has completed antibiotic treatment.

15. Action Statement
If a febrile infant is assessed as not requiring immediate antimicrobial therapy, then the likelihood of UTI should be assessed
If likelihood* is low (<1-2%), it is reasonable to follow the child clinically
If the likelihood is not low, there are two options:
Obtain specimen by catheter for UA ,UC
Obtain specimen by any means for UA and only culture those with positive UA
*LR: hx uti, t>39,FWLS,ill appearance, suprapubic tenderness, fever>24h, nonblack

16. Strong recommendation AAP 2011
If a clinician decides that a febrile infant with no apparent source for the fever requires antimicrobial therapy because of ill appearance or another pressing reason, a urine specimen should be obtained by catheterization for both culture and urinalysis before an antimicrobial is given.

17. Methods of Collecting Specimen
Bag urine:
Not suitable for culture
Negative culture rules out UTI, but
Positive culture likely to be false- positive
88% false-positive overall
Positive culture requires confirmation, which is not possible once antibiotic is started

18. Methods of Collecting Specimen
Catheterization
Compared to suprapubic aspiration:
Sensitivity = 95%
Specificity = 99%
Requires some skill, particularly in small infant girls. (Tip: If unsuccessful, leave catheter in.)

19. Methods of Collecting Specimen
Suprapubic aspiration: “Gold standard,” but
Variable success rates: 23–90% (higher with ultrasound guidance)
Requires technical expertise and experience
Often viewed as invasive
More painful than catheterization
May be no alternative in boys with severe phimosis or girls with tight labial adhesions

20. AAP 1999 guideline on childhood UTI was revised on 2011
Recommendatios on:
Diagnosis
Treatment
Imaging:
Follow-up
Guideline: Pediatrics. 2011;128(3):595–610
Technical report: Pediatrics. 2011;128(3):e749–e770

21. What’s New in This Revision
Diagnosis
Abnormal urinalysis as well as positive culture
Positive culture = ≥50,000 colony-forming units (cfu)/mL
Treatment: Oral as effective as parenteral
Imaging: Voiding cystourethrography (VCUG) not recommended routinely after first febrile UTI
Follow-up: Emphasis on urine testing with subsequent febrile illnesses

22. Enhanced Urinalysis Uncentrifuged urine >10WBC/mm3
Any number of organism in gram stain of Uncentrifuged urine

23. Atypical infection
Serious illness, poor urine flow , abdominal or UB mass, rise in Cr, septicemia, organism other than Ecoli , failure to respond within 48hrs

24. CASE 2: DX:complicated UTI
1months old ♂ with poor urinary stream and dribbling with refusal of feeding,+ Hx of Antenatal Hydronephrosis but no postnatal evaluation.
On PE: T=39ºand toxic, is not circumcised and has a distended urinary bladder and dribbling .U/A many WBC, Suprapubic U/C E-Coli10,000/ml,BUN and creatinine NL for age.
Sonography: bilateral hydroureteronephrosis, distended bladder,Lt kidney is smaller with ↓cortex.
DX:complicated UTI
Cont…

25. Rx: CASE 2: VCUG during treatment when U/C negative 1-Admission
2-Insert catheter (not Foley), start appropriate antibiotic(s) according to the antibiogram.
VCUG during treatment when U/C negative
And then….?

27. Complicated Vs Uncomplicated UTI
An uncomplicated UTI is one occurring in a normal host who has no structural or functional abnormalities, is not pregnant, or who has not been instrumented (for example, with a catheter).
All other UTIs are considered complicated

28. COMPLICATED UTI
Seriously ill, bactremia,↑Cr,non Ecoli organism,lack response to antibiotic within 48hr
Being male ,Age ≥65
Being pregnant
History of childhood UTIs
Acquiring a UTI while hospitalized
Having a urinary catheter or recent instrumentation
Obstruction or stone within the urinary tract, NGB, Enlarged prostate
high grade reflux
Having diabetes
Having a compromised immune system
Experiencing symptoms for more than 7 days before seeking treatment

29. RISK FACTORS FOR URINARY TRACT INFECTION:
Female gender
Uncircumcised male
Vesicoureteral reflux
Toilet training
Voiding dysfunction
Obstructive uropathy
Urethral instrumentation
Wiping from back to front in females
Bubble bath? Tight clothing
Pinworm infestation
Constipation ,Bacteria with P fimbriae
Anatomic abnormality (labial adhesion)
Neuropathic bladder , Sexual activity and Pregnancy

30. Case3:An 8 yr. old girl with dysuria,frequency,blood and clot passing + Hx of secondary Enuresis recently. +Hx of holding maneuvers
DX:???

31. Case 3 continued Clinical DX: hemorrhagic cystitis +DV* Plan: UA,UC
Empiric antibiotic Rx:
The most common cause : E-coli
hemorrhagic cystitis also caused by adenovirus 11 &21
*Dysfunctional voiding

32. FOLLOW UP OF A PATIENT WITH UTI
Why Follow UP:?
1)Risk of recurrence is high
2)Associated anatomical abn.

33. Recommendations from clinical practice guidelines for routine investigations in UTI
NICE 2007
AAP 2011
ISPN 2012
Age
< 6mo
6-36 mo
2-24 mo
2-36 mo
US during UTI
No unless poor resp . to Rx or atypical UTI
No unless atypical UTI
Yes if very unwell
Yes if poor response to Rx
Later US
Yes No
Yes *
Yes*
DMSA scan at 4-6 mo later
No unless atypical* UTI
No recommendation
No unless Abn. US/VCUG
VCUG
No unless atypical* UTI/Abn.US
No unless Abn.US, + FHx VUR*
No unless Abnormal US*
No unless Abnormal US
*NICE >3yr no investigation if response well within 48hr, US and DMSA scan for Atypical infection,US within 6wk of infection for recurrent infection and DMSA scan 6 mo later

34. RISK FACTORS:
Abnormal antenatal ultrasonogram of fetal urinary tract, family history of reflux, septicemia, renal failure, age younger than 6 mo in a male infant, likely family noncompliance, incomplete bladder emptying, no clinical response to appropriate antibiotic therapy within 72 hr, or infection with organism other than E. coli.

35. Atypical infection
Serious illness ,poor urine flow, abdominal or flank mass, elevated serum creatinine, septicemia , organism other than E.Coli, failure to respond within 48hrs

36. NICE guideline for children>3yrs
No investigation if responds well within 48hrs,
US :during infection in atypical UTI
US : within 6 weeks of infection in recurrent UTI
DMSA scan for atypical and recurrent infection mo after acute infection
VCUG: none

38. Of 1533 articles
325 full-text articles reviewed
33 studies met inclusion criteria
Children with an initial UTI
57% had changes consistent with acute pyelonephritis on the acute phase DMSA scan
15% had renal scarring on follow up DMSA scan

39. 2011 AAP Guidelines Evaluation of the Infant with Febrile UTI
Post-UTI evaluation
5) Infants with febrile UTI should have a renal and bladder ultrasound
6) VCUG should be deferred until the SECOND febrile UTI, unless the ultrasound is abnormal
Post-UTI management
7) Parents should be instructed to seek prompt evaluation for future febrile illnesses

41. Recommendation for US AAP:
Febrile infants with UTIs should undergo RBUS.
When:
Decide clinically: Within 48 hours if not responding to treatment as expected, unusually ill ; otherwise, when convenient.
US not needed if prenatal US in a reputable center is normal after 32weeks of gestation

42. Prophylaxis in UTI AAP 2011 and NICE guideline :
No routine recommendation for prophylaxis following 1st febrile UTI but may be warranted after recurrent UTI.

43. Prophylaxis in UTI Reflux Grade N Prophylaxis No Prophylaxis P None
# of Recurrences / Total N
None
373
7 / 210
11 / 163
0.15
Grade I 72
2 / 37
2 / 35
1.00
Grade II
257
11 / 133
10 / 124
0.95
Grade III
285
31 / 140
40 / 145
0.29
Grade IV
104
16 / 55
21 / 49
0.14
1,091

44. Indications and duration of prophylaxis
On patient age and presence or absence of VUR
-UTI below 1 yr of age while awaiting imaging
- VUR
-Frequent febrile UTI( >3 episodes in year)
- Not adviced in patients with urinary tract obstruction, urolithiasis and neurogenic bladder on CIC

45. ANTIBIOTIC PROPHYLAXIS
Medication and dose:
cotrimoxazole 1-2mg/kg Avoid in infants <3mo &G6PD def
nitrofurantoin 1-2 mg/kg
Vomiting and nausea,avoid in <3mo, G6PD def,renal insufficiency
cephalexin 10-15mg/kg in 1st 3-6 mo of life

46. Cranberry juice Cranberry juice Prevents bacterial adhesion
Prevents biofilm
formation

47. Risk of Renal Scarring by Number of UTIs
Scaring in UTI
Risk of Renal Scarring by Number of UTIs
Adapted from Jodul U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am. 1987;1(4):713–729

48. Risk Factors for Renal Scarring
• Recurrent febrile UTI
• Delay in treatment of acute infection
• Dysfunctional elimination
• Obstructive malformations
• VUR

49. Recommendation AAP
Following confirmation of UTI, parents or guardians should be instructed to seek prompt medical evaluation for future febrile illnesses to ensure that recurrent infections can be detected and treated promptly.

50. Points to remember UTI should be suspected in all cases of FWLS
• Most cases of UTI are simple, uncomplicated, and respond readily to OPD antibiotic RX without further sequelae.
• Appropriate treatment, imaging, and follow-up prevent long-term
sequelae in patients with more severe infections or chronic infections.
• Any child with proven UTI should have imaging studies performed to
R/O VUR or other renal anomalies

51. Recurrent UTI Elimination disorders, encopresis and enuresis
Constipation
Holding maneuvers
Infrequent voiding
 VUR
NGB
NON-NEUROGENIC NGB

54. Spinning top deformity

55. PREVENTION OF RECURRENT UTI
• GENERAL
• Adequate fluid intake, frequent voiding, avoid constipation
• Regular and volitional low pressure voiding
with complete bladder emptying
• Double voiding
• circumcision
Treatment of dysfunctional voiding

56. Age < 2mo
See the list below:
Cefotaxime 150 mg/kg/day IV/IM divided q6-8h
Ceftriaxone 75 mg/kg/day IV/IM as a single dose or divided q12h (ceftriaxone should not be used in infants younger than 6wk) or
Ampicillin 100 mg/kg/day IV/IM divided q8h plus  gentamicin 3.5-5 mg/kg/dose IV q24h if patient younger than 7d, otherwise gentamicin mg/kg/dose IV q24h
Transition to oral antibiotic active against the offending organism after 24-48h for total of 14d course
Age 2mo to 18y
Outpatient therapy:
Nitrofurantoin 5-7 mg/kg PO divided q6h for 3-10d orContraindicated in Children < 3 months of age or when GFR < 50% or in children with G6PD deficiency
Should not be used in children with symptoms consistent with pyelonephritis as it is poorly concentrated in the bloodstream and has poor tissue penetration or
Trimethoprim (TMP) and sulfamethoxazole 6-12 mg/kg/day PO divided q12h, based on TMP component orContraindicated in children < 6 weeks of age
Sulfisoxazole mg/kg divided q 6h or
Amoxicillin clavulanic acid  mg/kg/day divided q8h or
Cephalexin  mg/kg/day divided q6h or
Cefixime 8 mg/kg/day q 24h or
Cefpodoxime 10 mg/kg/day divided q 12h or
Cefprozil 30 mg/kg/day divided q 12h or

57. Cefuroxime axetil 20-30 mg/kg/day divided q12h
Studies have shown oral antibiotics to be as effective as IV antibiotics in most cases of simple pediatric cystitis
Most children may be treated with oral medications; those deemed “toxic” or are unable to retain oral intake may require parental treatment
Short-course (3d or 5d) oral antibiotic therapy has been shown to be as effective as 10-d or 14-d courses for nonfebrile UTIs
For febrile UTIs, the minimum treatment duration should be 7d and may extend to 10-14d
Inpatient therapy:
Ceftriaxone 75 mg/kg/day IV/IM every 24h or
Cefotaxime 150 mg/kg/day IV/IM divided q6-8h or
Ceftazidime mg/kg/day divided q8h or
Ampicillin 100 mg/kg/day IV/IM divided q8h plus  gentamicin 7.5 mg/kg/day IV divided q8h or
Tobramycin 5 mg/kg/day divided q8h or
Piperacillin 300 mg/kg/day divided q 6-8h
Transition to oral antibiotic active against the offending organism after 24-48h