1. Urinary Tract Infection in Children Amalia Guardiola Joint Primary Care Fellow Nov. 17, 2005

2. Overview ► Definition ► Classification – Lower v.s Upper infection ► Signs and Symptoms ► Physical Exam ► U/A and Urine Cx ► Mechanism of Disease – common pathogens ► Treatment – Prophylaxis ► Imaging ► Follow up

3. UTI ► Definition  Infection of any component of the urinary tract including ► Urethritis ► Cystitis ► Pyelonephritis

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

5. Clinical Presentation ► Age and gender dependent ► 0 - 2 months:  Fever ► 2 mo.– 2 y/o:  Fever (>38 C)  Irritability  Vomiting and Diarrhea  Decrease apetite  Between 1-2 y/o = crying on urination, foul smelling odor

6. 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

7. Urethritis ► In female infants  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

8. 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

9. Cystitis ► Afebrile usually ► Frequency ► Enuresis ► Dysuria ► Reluctance to void

10. 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

11. 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

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

13. Prevalence ► UTI may be source of infection in 5-10% of febrile infants and toddlers  May be missed when URI or OM is deemed the focus (concomitant disease is misleading)  Rec. urinary screening in girls < 2 y/o and boys < 1 y/o ► Peak ages 1-24 months

14. Prevalence ► Less than a year of age: Girls 6.5% Boys 3.3%

15. Prevalence 1-2 years ► Girls 8.1%  White > black ► Boys 1.9% ► Circumcised boys overall 0.2-0.4% therefore 15-20 times less than uncircumcised boys

16. Mechanism of Disease ► Predisposing factors:  Congenital structural abnormalities  Hx of broad spectrum antibiotics  Incomplete emptying or infrequent voiding  Constipation  Immaturity of host defense

17. Mechanism of Disease ► Usually an ascending infection  Short urethras in females and infant boys  Fecal soiling  Turbulent flow  Voiding dysfunction  Sex or manipulation

18. Mechanism of Disease ► Most common organisms: E. coli, Enterococcus, Proteus  Staph. Saprophyticus is common in adolescent females

19. Mechanisms of disease ► Hematogenous spread unusual except  Neonates (GBS, E. coli, Listeria)  GI disease with peritonitis, sepsis  Severely ill children with multiorgan disease  Urinary catheter presence

20. Physical Examination ► Physical findings in pyelonephritis  Irritability  Abdominal examination ► tenderness not limited to suprapubic area in infants and preschoolers  Back examination ► CVA tenderness

21. Physical Examination ► MUST do a genital examination for children with abdominal pain or urinary tract symptoms ► Common findings  Erythema secondary to vulvovaginitis  Possible foreign body (external retained toilet paper)  Evidence of sexual abuse (disrupted hymen, discharge)  Pinworms  Circumcision status  Labial adhesions  Prolapsed urethra

22. 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

23. 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)

24. 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)

25. 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”

26. 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)

27. Sensitivity and Specificity of Components of the UA Test Sensitivity % (Range) Specificity % (Range) 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)

28. 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

29. 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

30. 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

31. 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

32. Antibiotic Choice ► Older infants and children, E. coli, Klebsiella sp., & Proteus sp. are among the most common organisms  Treat based on resistance patterns in the community in which you practice  Hospitals and the Health Department are good sources of information

33. 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

34. Prophylaxis ► Amoxil is often an empiric choice in Houston  10-20 mg/kg/day ► May use Bactrim, but not in children <6 wks old  competitive inhibition of bilirubin metabolism  2-4 mg/kg/day ► Nitrofurantoin (Macrodantin)  1-2 mg/kg/day

35. Infants ► Oral treatment if  Non-toxic appearing  Taking oral fluids and meds well  Resources to purchase antibiotics  Ensure close follow-up in 24-72 hrs as outpatient (telephone, transportation and conscientious parents)  Ensure imaging as outpatient

36. Children and Adolescents ► Oral antibiotics are usually fine  Non-toxic  Close follow-up ensured ► Choice of antibiotics often includes fluoroquinolones (currently off-label) but approval anticipated

37. Adolescent Females ► Strongly consider empiric therapy for STD if sexually active and symptoms of cervicitis pending cultures of urinary and genital tract ► Consider same in adolescent males with urethritis

39. IMPORTANT POINT ► One implication in the febrile young infant or small child is that pyelonephritis may signify a structurally or functionally abnormal urinary tract that contributes to ascending infection

40. The Abnormal Urinary Tract ► Structural Abnormalities  Posterior urethral valves  Uretero-pelvic junction obstruction  Uretero-vesicular junction obstruction  Polycystic kidney  Duplication of collecting system  Duplication of ureters  Ectopic ureters

41. Functional Abnormalities ► Vesicoureteral Reflux  In infants less than 1 y/o rate may exceed 50% ► Voiding disorders ► Relation of UTI to  Constipation  Encopresis  Enuresis

42. Imaging ► All boys with a febrile UTI should be imaged ► Girls < 36 months ► Girls 3-7 y/o with febrile UTI or recurrent UTI

43. Imaging ► Ultrasound  Detects structural malformations  Helpful in detecting the ureteral dilatation of advanced stage reflux (Grades III-IV)  Can be done imediately

44. Imaging ► VCUG (CONTROVERSIAL)  Bladder is fully filled via catheter with radiopaque liquid  Child is asked to void  During voiding, look under fluoroscopy for reflux  Can be done after 48 hrs of receiving antibiotics  Can be done 4 – 6 weeks after UTI

45. Imaging ► Radionuclide Cystogram (RNC)  Nuclear study comparative to VCUG  Diagnoses obstruction  Only for girls  May use Lasix ► DMSA scan  Looks for scarring  Differentiates acute pyelo v.s. cystitis  Done at 6 mo

47. Vesicoureteral Reflux ► Patients with high grade relfux are 4-6 times more likely to develop renal scarring than those with low grade VUR and 8-10 times more likely than people without reflux

48. Vesicoureteral Reflux ► Grade I-reflux without dilatation into distal ureter ► Grade II-reflux with dilatation into proximal ureter ► Grade III-reflux into renal pelvis with dilatation ► Grade IV-Further dilatation and distortion of calyces ► Grade V- Hydronephrosis

49. Normal kidney, ureter, and bladder

50. Grade I Vesicoureteral Reflux: Urine (shown in blue) refluxes part-way up the ureter.

51. Grade II Vesicoureteral Reflux: Urine refluxes all the way up the ureter.

52. Grade III Vesicoureteral Reflux: Urine refluxes all the way up the ureter with dilatation of the ureter and calyces (part of the kidney where urine collects).

53. Grade IV Vesicoureteral Reflux: Urine refluxes all the way up the ureter with marked dilatation of the ureter and calyces.

54. Grade V Vesicoureteral Reflux: Massive reflux of urine up the ureter with marked tortuosity and dilatation of the ureter and calyces.

55. Approach to Reflux ► Antibiotic Prophylaxis  Controversial re: duration  For low grade reflux (Grade I-II) may need it for one year until VCUG is repeated  For high grade reflux (III or above) may need it for 2 years until VCUG is repeated  Need randomized controlled studies

56. Purpose of prophylaxis ► Prevention of bacteriuria ► Not targeted at last infection which is presumed to be eradicated but rather targeted at normal gut flora ► Resistance may be important consideration but still want to use narrow spectrum to avoid increasing resistance.

57. Antibiotic Prophylaxis ► Amoxil 20 mg/kg per day; if given at bedtime takes advantage of normal nocturnal urinary concentration overnight and in toilet trained kids, retention of antibiotic in the bladder overnight ► Bactrim ► Macrodantin

58. Surgery for Reflux ► Now increasingly controversial ► Was recommended for high grade reflux ► Involved ureteral re-implantation  Pathogenesis of reflux was believed to be two- fold ► True faulty implantation with decreased angle of implantation at UVJ ► Histologic abnormality of smooth muscle junction

59. Ureteral Reimplantation ► Not worth the risks in very advanced reflux with renal parenchymal damage ► Invasive ► Adhesions and scar tissue may result in re- occurrence of reflux or obstruction

60. DMSA scan ► Evaluates percent function of renal parenchyma and shows SCARRING ► Useful to determine utility/risk/benefit of surgery in structurally abnormal kidney or advanced reflux ► May be done in anyone over the age of one month ► No evidence base for real risk benefit

61. Consults ► Urology  structurally abnormal urinary tract  advanced stage reflux ► Nephrology  hypertension associated with renal disease  renal functional impairment

62. Role of Primary Care Physician ► Vigilance for UTI during febrile illnesses including URI, OM ► Monitoring of urine with UA and culture  May repeat U/A after finishing abx (10-14 days) ► Monitoring of prophylaxis and renal function  Adjust prophylaxis for weight

63. Summary ► Definition ► Classification – Lower v.s Upper infection ► Signs and Symptoms ► Physical Exam ► U/A and Urine Cx ► Mechanism of Disease – common pathogens ► Treatment – Prophylaxis ► Imaging ► Follow up

64. THE END Questions?

65. Bibliography ► UTI Guideline Team, Cincinnati Children’s Hospital Medical Center. www.cincinnatichildrens.org/svc/dept-div/health- policy/ev-based/uti.htm. www.cincinnatichildrens.org/svc/dept-div/health- policy/ev-based/uti.htm. www.cincinnatichildrens.org/svc/dept-div/health- policy/ev-based/uti.htm. ► Homer CJ, et. al.Practice Parameter: The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. Apr 1999;103 (4) 843-52 ► Hoberman A, et. al. Is urine culture necessary to rule out urinary tract infection in young febrile children?Pediatric Infectious Disease Journal. Apr 1996; 15 (4) 304-9 ►

66. Bibliography ► Hoberman A, et al. Prevalence of UTI in febrile infants. July 1993; 123 (1) 17-23 ► Hoberman A, et al. Oral v.s Initial Intravenous Therapy for UTI in Young Febrile Children. Pediatrics. July 1999; 104 (1) 79-86 ► Hoberman A. et al. Imaging studies after a first febrile UTI in Young Children. Jan 2003; 348 (3) 195-202