Pediatric Urinary Tract Infections

1. Pediatric Urinary Tract Infections Eddie Needham, MD, FAAFP Program Director Emory Family Medicine Residency Program

2. Objectives Define Urinary Tract Infection (UTI) List antibiotic treatment options for UTI List the workup after a first febrile UTI Be familiar with the rationale for using prophylactic antibiotics after the first febrile UTI

3. Case 1 A four year old previously healthy girl presents to clinic with c/o dysuria. She has no fever and has a stable home with reliable parents. Immunizations are UTD. UA shows + Nitrites and + LE WBC – unknown because we don’t currently spin our own urines at Dunwoody.

4. What is your plan? • Urine culture? • Antibiotics? • Rocephin in clinic? • Oral antibiotics? • Admit to the hospital? • Work up (We’ll define this later)?

5. Case 2 An 18 month old female presents with increased irritability x 3 days, subjective fevers, and decreased appetite. PMHx – usual childhood illnesses – AOM x 1, URIs x 2, AGE x 1. Benign recoveries. Immunizations are up-to-date (UTD) Good social support

6. Case 2 - Exam Vital Signs – normal for age except T 102.5 General appearance – fussy, easily consolable, nontoxic HEENT – normal with clear pharynx and TMs AU Lungs - CTA CV – normal Abdomen – soft Skin – no rash

7. Fever without a Source Guideline

8. Clinic Management • Draw blood for CBC and potentially a blood culture? • Urine culture? • Antibiotics? • Rocephin in clinic? • Oral antibiotics? • Admit to the hospital? • Work up (We’ll define this later)?

9. Clinic workup Are you able to draw blood? Can you perform a bladder catheterization? Two Q-tip technique for little girls

11. Evaluation • Your catheter UA confirms the diagnosis. • You send the urine for culture. • What now? • Child admitted? • Child goes home? • What does the evidence say?

12. Pediatric UTIs and EBM • Up to 7% of girls and 2% of boys experience a symptomatic culture-proven UTI prior to 6 years of age. • Of febrile neonates, up to 7% have UTIs. • (See Fever without a source guidelines) • Most UTIs in children are from ascending bacteria • E. coli (60-80%), Proteus, Klebsiella, Enterococcus, and coag. neg. staph.

13. Epidemiology The overall prevalence of UTI is approximately 5 percent in febrile infants but varies widely by race and sex. Caucasian children had a two- to fourfold higher prevalence of UTI as compared to African-American children Females have a two- to fourfold higher prevalence of UTI than do circumcised males Caucasian females with a temperature of 39 ºC have a UTI prevalence of 16 percent

14. Approximate probability of urinary tract infection in febrile infants and young children by demographic group Data from:Hoberman, A, Chao, HP, Keller, DM, et al. Prevalence of urinary tract infection in febrile infants. J Pediatr 1993; 123:17.Shaw, KN, Gorelick, M, McGowan, KL, et al. Prevalence of urinary tract infection in febrile young children in the emergency department. Pediatrics 1998; 102:e16.

15. Definition of UTI on culture Hillerstein S. Recurrent urinary tract infections in children. Pediatr Infect Dis 1982; 1:275.

16. Symptoms • Classic UTI symptoms in older children • Dysuria, frequency, urgency, small-volume voids, lower abdominal pain. • Infants with UTIs have nonspecific symptoms • Fever, irritability, vomiting, poor appetite

17. Neonatal hematuria? Nope, it’s uric acid crystals

18. Evaluation In children with a high likelihood of UTI, a urine culture is required. In children with a low likelihood, a negative dipstick in a clear urine reduces the need for culture. If the dipstick shows (+) LE and/or (+) Nitrites, send a urine culture. The dipstick is not sufficient to diagnose UTI’s because false positives can occur.

19. Urine dipsticks In a cohort study with an 18% baseline prevalence of UTI, negative LE and nitrates on dipstick had a negative predictive value of 96%. NPV = True negative _________________ True negative + false negative

20. Leukocyte Esterase and Nitrites • LE is produced from the breakdown of leukocytes. Not always indicative of infection • Vaginitis/vulvitis can lead to inflammation without infection  + LE • Nitrites are produced by bacteria that metabolize nitrates: E. coli, Klebsiella, Proteus (GNRs) • Much more predictive of UTI • GPCs do not produce nitrites

21. Blood cultures Blood cultures are generally unnecessary in most children with UTI. They are more frequently positive in children younger than two months whose urine grows Group B strep or Staph. Aureus. In general, we’ll send febrile children less than two months old to the ER for emergent evaluation/labs.

22. Treatment of UTIs Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999;104:79-86. Baker PC, Nelson DS, Schunk JE. The addition of ceftriaxone to oral therapy does not improve outcome in febrile children with urinary tract infections. Arch Pediatr Adolesc Med 2001;155:135-9. The efficacy of oral regimens is as effective as parenteral regimens - this is great news for outpatient therapy  If the child is not responding the empiric treatment within two days while awaiting culture results, repeat the urine culture and perform a renal ultrasound.

23. Antibiotic Choices • Trimethoprim-sulfamethoxizole is a good choice after two months of life • Other choices: • Amoxicillin – some resistance with E. coli • Cephalosporins: cefixime (Suprax), cefpodoxime (Vantin), cefprozil (Cefzil), loracarbef (Lorabid) • No cephalosporins cover enterococcus • Treat for 7-14 days. One day course not effective.

24. Further testing/work-up After the UTI resolves, what type of workup should ensue?

25. 1999 Clinical Practice Guidelines from the AAP Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. [published corrections appear in Pediatrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediatrics 1999;103:843-52. • Routine imaging for children two months to two years of age is recommended. • Ultrasound all children with febrile UTIs • Consider VCUG/Renal scintigraphy

26. Newer information Zamir G, Sakran W, Horowitz Y, Koren A, Miron D. Urinary tract infection: is there a need for routine renal ultrasonography? Arch Dis Child 2004;89:466-8 255 children < 5 years old admitted with their first uncomplicated febrile UTI (pyelo) Renal ultrasound did not change management

27. Newer Information 150 children 2 – 10 years old with first UTI were randomized to routine imaging (U/S and VCUG) or to selective imaging (for recurrent UTI or persistent problems) 21 % (1 in 5) in the selective group had imaging performed Routine imaging increased the use of prophylactic antibiotics (28% vs 5%) No change in rate of recurrent UTIs (26% vs 21%) No change in rate of renal scarring (9% vs 9%) Dick PT. Annual Meeting of Canadian Pediatric Society, June 12-16, 2002. Pediatric Notes 2002;26(27):105

28. Vesicoureteral Reflux and Treatment Nuutinen M, Uhari M. Recurrence and follow-up after urinary tract infection under the age of 1 year. Pediatr Nephrol 2001;16:69-72 Approximately 40% of children with febrile UTIs have VUR. Approximately 8% of children with febrile UTIs demonstrate renal scarring when studied. Treatment recommendations are made to stop the progression of VUR with medications/antibiotics and/or surgery. No data/EBM demonstrate that treatment of VUR prevents renal scarring, hypertension and CKD

29. Antibiotic prophylaxis • Children with VUR are treated prophylactically with antibiotics to prevent potential renal scarring. • Nitrofurantoin or trimethoprim-sulfamethoxizole • Half the standard dose administered at bedtime • Family physicians would generally have a pediatric urologist involved to assist in making treatment decisions.

30. How long to continue Abx? Cooper CS, et al. The outcome of stopping prophylactic antibiotics in older children with vesicoureteral reflux. J Urol 2000 Jan;163(1):269-72; discussion 272-3. Although the evidence is not conclusive, it appears the risk of scarring diminishes with age. Accordingly, some experts recommend cessation of prophylaxis after age 5 to 7 years, even if low-grade VUR persists. In one study of 51 low-risk (no voiding abnormalities or renal scarring) older children (mean age 8.6 years) with grades I to IV VUR, cessation of prophylactic antibiotics resulted in no new renal scarring on annual DMSA

31. Indications to order radiologic studies Up To Date – accessed September 12, 2007 Children younger than 5 years of age with a febrile UTI Girls younger than 3 years of age with a first UTI Males of any age with a first UTI (PUV) Children with recurrent UTI Children with UTI who do not respond promptly to therapy

32. Studies to consider • Renal Ultrasound • Will evaluate for perinephric abscess in patients not responding to antibiotics. • Can evaluate for hydronephrosis/hydroureter • Of note, dilation of the kidneys and ureters can easily be seen on routine anatomy scans during pregnancy. • Picking up vesicoureteral reflux while asymptomatic • Does this help or hurt? Staging of VUR, antibiotics, etc...

33. Hydronephrosis

34. Male with the findings below.Cause?

37. Studies to consider • Voiding cystourethrogram – two techniques • One involves fluoroscopic contrast – more radiation but better delineation of anatomy for grading VUR • The other uses a radionuclide – less radiation and more sensitive than contrast

38. Normal VCUG

39. Vesicoureteral reflux (VUR)

40. Megaureter

41. Studies to consider • Renal scintigraphy using dimercaptosuccinic acid (DMSA) • Can detect scarring in the kidneys. • Renal cells take up the tracer. • Those cells damaged by pyelonephritis or scarring do not take up the tracer. • Management or followup of patients does not change in most cases. • Thus, not generally used for initial evaluation.

42. Scar in the superior and inferior pole of the right kidney

43. Myths Bathing in bubble baths causes UTIs Wiping back-to-front causes UTIs Cranberry juice helps UTIs – only proven to be of minimal benefit in adult women. No proven benefit to children

44. VUR Treatment 1997 AUA guidelines Elder JS, et al. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children, J Urol 1997 May;157(5):1846-51. Children younger than 1 year of age, regardless of grade of reflux, should be treated medically, as they have a high likelihood of spontaneous resolution. Surgery is a reasonable option if they have grade V reflux and renal scarring. All patients with grade I or II reflux, either with unilateral or bilateral disease, should be treated medically, as they have high likelihood of spontaneous resolution. Children between 1 and 5 years of age with grade III or IV reflux, either unilateral or bilateral disease, should be treated medically. Surgery is a reasonable option if there is bilateral reflux and renal scarring. Children between 1 and 5 years of age with grade V, either unilateral or bilateral disease, without renal scarring, can be treated medically. If there is renal scarring, surgery is recommended for both unilateral and bilateral disease.

45. VUR Treatment Children 6 years or older with unilateral grade III to IV reflux without renal scarring can be treated medically. If the reflux is bilateral and/or there is renal scarring, surgical treatment is recommended. Children 6 years or older with grade V reflux should be treated surgically with or without evidence of renal scarring, as their reflux is unlikely to resolve spontaneously. Surgery also should be considered if medical therapy fails either because of poor compliance, breakthrough infections on account of antibiotic resistance, or significant antibiotic side effects. Finally, consideration of patient and parent preference is important in the final decision.

46. So, back to our cases…

47. Case 1 A four year old previously healthy girl presents to clinic with c/o dysuria. She has no fever and has a stable home with reliable parents. Immunizations are UTD. UA shows + Nitrites and + LE WBC on UA– unknown.

48. What is your plan? • Urine culture? • Antibiotics? • Rocephin in clinic? • Oral antibiotics? • Admit to the hospital? • Work up (We’ll define this later)?

49. EBM answer She is afebrile – no need for radiologic studies Send the urine for culture Start empiric antibiotics for 7-14 days

50. Case 2 An 18 month old female presents with increased irritability x 3 days, subjective fevers, and decreased appetite. PMHx – usual childhood illnesses – AOM x 1, URIs x 2, AGE x 1. Benign recoveries. Immunizations are up-to-date (UTD) Good social support