Urinary Tract Infections in Children: What We Know and What We Don t

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Ellen Lucas
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1 Urinary Tract Infections in Children: What We Know and What We Don t Daniel Hirselj, MD Northwest Urology, LLC North Pacific Pediatric Society Conference April 29, 2017

2 Urinary Tract Infections in Children: What We Know and What We Don t The Basics Current Guidelines/Recent Research Gray Areas Discussion/Questions

3 Epidemiology: Affects 3% of children Accounts for 1,000,000 office visits yearly Accounts for 13,000 hospital admissions yearly Estimated yearly health care cost: $180M 2 nd most common bacterial infection seen in children (URI)

4 Epidemiology: In 1 st year of life: male-to-female ratio 2.5:1 After 1 st year of life: male-to-female ratio 1:20 Uncircumcised male-to circumcised male 10:1 Risk of UTI in uncircumcised boys, though highest in 1 st year of life, REMAINS higher throughout childhood (and adulthood) High rate of recurrence throughout childhood Between 25% (males) and 50-60% females

5 Etiology: SEEKS PP S erratia E. coli E nterococcus K lebsiella S taph P roteus P seudomonas

6 Goals of Treatment/Management #1: detect urinary tract pathology early - risk of renal scarring from reflux-related infections highest in infancy #2: avoid renal damage - uremia - HTN - PTL/toxemia of pregnancy VUR: 4 th most common cause of renal failure requiring transplantation in children Reason why pediatric urology exists!!

7 What are the signs/symptoms?

8 Most important symptom: FEVER

9 Host factors: Perineal colonization of intestinal flora is primary cause of infection Short urethral length in females secondary factor Foreskin also a secondary factor Hematogenous seeding of urinary tract is RARE (results in abscess)

15 Once bacteria gain entry into bladder Bacterial/host interactions required to turn a nuisance into a problem Cell surface adhesion molecules Fimbria Affinity for mannose (and mannose receptors found on uroepithelium) VUR (less pathogenic bacteria, easy access)

16 Though we worry about early identification of children with VUR, over 50% of children with pyelonephritis DO NOT have VUR

19 Management of VUR important, but preventing/limiting bacteriuria is the FIRST LINE of defense Recurrent pyelonephritis, not persistent VUR, is the cause of acquired renal scars sterile VUR is not harmful to the kidneys in children

21 As urologists, our primary interest is in identifying those children who may require short-term, long-term surveillance or surgical management of their UTIs In the overwhelming majority of these children, they will present with FEVER Once they present, what to do next???

22 Current Research/Guidelines Society for Pediatric Urology American Academy of Pediatrics

23 Reaffirmation of AAP Clinical Practice Guideline: The Diagnosis and Management of the Initial UTI in Febrile Infants and Young Children 2-24 months of Age Pediatrics 2016; 138 Updated review of 2011 CPG from UTI subcommittee Establishment/reiteration of seven Key Action Statements

24 AAP CPG 2016 Action Statement 1: In child with unexplained fever, if decision made to start antibiotics, the clinician should obtain urine specimen for U/A and culture prior to administering antibiotics Specimen should be obtained via SPA or catheter, as bag specimen is not a reliable collection method

25 AAP CPG 2016 Action Statement 2: In infant with unexplained fever deemed nontoxic and not requiring antibiotics promptly, clinician should assess likelihood of UTI If low index of suspicion, then monitoring without testing OK If high index of suspicion, then two options: Cath or SPA U/A and culture Convenient U/A first, then cath or SPA U/A and culture if suspicious

26 AAP CPG 2016 Action Statement 3 A diagnosis of UTI requires both a urinalysis with pyuria and/or bacteriuria AND the presence of 50,000cfu/cc of uropathogen in an appropriately-obtained culture specimen

27 AAP CPG 2016 Action Statement 4: Clinician should base choice or route of antimicrobials on practical grounds Oral or IV is equally efficacious Guided by sensitivities 7-14d treatment decided by clinician

28 AAP CPG 2016 Action Statement 5: Infants with febrile UTI should undergo renal and bladder ultrasound U/S can identify most (but certainly not all) children at risk for renal scarring Not effective at predicting presence or severity of VUR

29 AAP CPG 2016 Action Statement 6: VCUG should not be routinely performed after first febrile UTI Indicated if U/S demonstrates hydronephrosis, scarring or other abnormality suggestive of highgrade VUR or obstructive uropathy Further evaluation (VCUG) should be conducted for recurrent, febrile UTI

30 AAP CPG 2016 Action Statement 7: In child with history of febrile UTIs, clinician should instruct parents to seek prompt medical evaluation for child with unexplained fever (within 48 hours) Important to diagnose and treat febrile UTI promptly Particularly important in infants (when risk of renal scarring is highest)

31 Antimicrobial Prophylaxis for Children NEJM, 2014: 370 with Vesicoureteral Reflux Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) Study 2-year, multisite, randomized, placebo-controlled trial 607 children diagosed with VUR following febrile OR symptomatic UTI ½ given prophylaxis (Septra), ½ given placebo Evaluation of prophylaxis and subsequent prevention of recurrent UTIs (primary) Renal scarring, antimicrobial resistance, and prophylactic failure (secondary endpoints)

32 RIVUR Trial Data collected at 19 sites nationwide Age range 2-71 months (average age 12 months) Children followed with DMSA renal scans at 0, 1, 2 years Children followed with VCUG at 0, 1, 2 years UTI: culture proven (50K or greater) NO BAGS ALLOWED! Failure: defined as 2 febrile UTIs or 1 febrile UTI + 1 symptomatic UTI or 4 symptomatic UTIs Rectal swabs to detect Septra-resistant E. coli

34 RIVUR Trial 91% female 80% Caucasian Median age: 12 months 80% with grade II-III VUR 48% with bilateral VUR NOTE: grade V VUR excluded from study 56% with association bowel dysfunction/constipation (though not clear how defined)

35 RIVUR Trial RESULTS: 111 children with 171 recurrences (72% febrile) Risk of recurrence decreased by 50% in children with prophylaxis Risk continued to decrease throughout the study period No difference in incidence of renal scars (10% vs 12%) Children with III-IV VUR more likely to have febrile recurrence than I-II VUR (23% vs 14%) Recurrence more common in children with underlying bowel-bladder dysfunction VUR spontaneously resolved in 51% of children

36 RIVUR Trial

37 RIVUR Study Findings somewhat counter to previous studies, which demonstrated no effect with prophylaxis ALSO: Grade V VUR not included Effect of scarring possibly affected by stringent evaluation/follow-up 8 children x 2 years to prevent 1 febrile UTI

38 Current Management Strategies (according to me)

39 History and Physical Assessment of symptoms/signs Assoc bowel issues (constipation/encopresis) Assoc daytime continence issues Voiding frequency, stooling frequency EXAM: CVA tenderness, suprapubic tenderness, palpable stool, sacral dimple/tuft, warm-to-touch

40 Again, it is important to delineate between FEVER and ALL OTHER SIGNS/SYMPTOMS, as unexplained fever is symptom most associated with GU pathology (VUR, obstructive uropathy) - body s response to cystitis is (almost) never fever >

41 Laboratory Evaluation U/A and urine culture Collection method Clean catch Cath SPA Bag (NEVER EVER EVER EVER EVER)

42 Once child diagnosed with culture-proven FEBRILE UTI, imaging required in smaller children/infants/circumcised boys, evaluation will include renal/bladder ultrasound, VCUG (with/without sedation) Sedation usually in children > 18mos of age (Versed, nasal nitrous oxide) General anesthesia not recommended (bladder needs to be awake In some instances nuclear medicine renal scan is used to assess for scars

44 Bottom Up Evaluation vs. Top Down Evaluation Bottom Up: U/S and VCUG first, then nuclear medicine to assess upper urinary tracts for scars Nuclear medicine reserved for those children with abnormalities on U/S, high-grade VUR (or other determinant) Most common

45 Important considerations with Bottom Up evaluation: Normal U/S does NOT equal no VUR High grades of VUR can spontaneously resolve (more common in infant boys) Timing of VUR during filling/voiding cycle is important (IMO)

46 Top Down Approach: Nuclear medicine renal scan done first Presence of renal scars is most important piece of data to determine need for intervention This can be done in concert with U/S VCUG reserved for those children with abnormalities found on nuclear medicine More recently popular, now fading Anesthesia for nuclear medicine, shortage of radiotracer, NUCLEAR or UNCLEAR medicine

47 Follow-up in Children with UTIs If NOT FEBRILE or FEBRILE WITHOUT VUR: Aggressive management of local factors to prevent/limit bacteriuria Bowel mgmt, meticulous hygiene, timed voids, good toilting posture In severe bowel bladder dysfunction (BBD) with recurrent, febrile UTIs, prophylaxis possible» PIC cystogram/cystoscopy for occult VUR Pelvic floor re-training (PT) GI referral (encopresis)

48 Follow-up in Children with UTIs If FEBRILE WITH VUR: Routine/surveillance US (Q3, 6, 12 mos.) Routine/surveillance VCUG (Q12-24 mos.) +/- prophylaxis (grade/laterality of VUR, U/S findings, age, circ status, family dynamic) Discussion regarding circumcision in uncircumcised boys Circ as effective (or more) in preventing UTIs Nuclear Medicine to confirm changes on U/S (or to push toward or away from surgery

49 Who needs Surgery? Surgical success with open reimplantation: approaching 100% (90% with grade V VUR) Surgical success with endoscopic correction of VUR (Deflux procedure): 40-85% (gradedependent, surgeon-dependent) Rate of spontaneous resolution > 50%

50 Who Needs Surgery? Grade V VUR after 1 year of age Persistent high-grade VUR through toddlerhood Breakthrough infections with VUR Worsening/stagnant renal growth on serial U/S despite no documented UTIs Worsening VUR on serial VCUGs despite no documented UTIs Untrustworthy family in high-risk child Family says, enough is enough

51 New Frontiers in UTI management Basic science research (cell level, adhesion molecule targeting, pharmacotherapy) Imaging (MR urography, sedation protocols) Surgical (robotic surgery)

52 Summary: UTIs in children affect all of us, every day We must identify those who need specialist evaluation We must provide effective, efficient care We must avoid the avoidable

UTI are the most common genitourinary disease of childhood. The prevalence of UTI at all ages is girls and 1% of boys.

UTI are the most common genitourinary disease of childhood. The prevalence of UTI at all ages is girls and 1% of boys. 1-3% of Below 1 yr. male: female ratio is 4:1 especially among uncircumcised males,