Advanced Pediatric Emergency Medicine Assembly

(+)Kathy Shaw, MD, FACEP Associate Chair and PSO, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania; Nicolas Crognale Endowed Chair and Chief, Division of Enmergency Medicine, Children's Hospital, Philadelphia, Pennsylvania Advanced Pediatric Emergency Medicine Assembly March 23-26 2015 New York, NY Best Practice UTI The 2011 guidelines that were published in Pediatrics recommended many changes in our approach to the child with a first febrile UTI. No longer are prophylactic antibiotics routinely recommended nor is admission to the hospital routine. The emergency medicine provider is now often responsible for orchestrating outpatient follow-up of these children. The AAP guidelines will be reviewed with particular emphasis on how emergency care including parental education is impacted. OBJECTIVES Describe emergency management of children with suspected UTI including who is at risk Outline how to counsel parents about future steps for their child with a UTI Discuss need for follow-up testing and referral including the role of ultrasound in the management of a child with a febrile UTI and when to order an outpatient VCUG 3/25/2015 4:45 PM-5:15 PM Sutton Complex WE-19 DISCLOSURES: (+) No significant financial relationships to disclose

New York March 2015 Best Practice UTI: Recommendations for screening, treatment and follow-up ACEP s PEM Assembly Kathy N. Shaw, MD, MSCE Nicholas Crognale Endowed Chair Chief, Division of Emergency Medicine The Children s Hospital of Philadelphia Professor of Pediatrics University of Pennsylvania Perelman School of Medicine Associate Chair for Quality and Patient Safety Department of Pediatrics Detecting UTI in Febrile Infants 2-24 months of age 1

Detecting UTI in Febrile Infants 2-24 months of age Symptoms - non-specific Other potential sources may be present Screening can be time consuming, uncomfortable, costly ED screening for UTI variable Overall Prevalence 2%-10% in most studies Detecting UTI in Febrile Infants 2-24 months of age Why worry? UTI Morbidity Urosepsis: Life threatening but rare beyond neonatal period; associated with congenital abnormalities Febrile UTI = pyelonephritis (+nuclear scan 60-90%) Pyelonephritis renal scarring, (15%-50%) which may be associated with HT, ESRF Detection, early treatment, renal ultrasound, and F/U 2

Importance of Early Diagnosis and Treatment? DMSA results in the acute phase and day of treatment Doganis, D. et al. Pediatrics 2007;120:e922-e928 Copyright 2007 American Academy of Pediatrics Risk of End Stage Renal Failure (ESRF) after pediatric UTI? Data from renal registries from Europe, Australia, New Zealand, the United States, and the United Kingdom Estimated Risk of ESRF: 1 in 154 to 1 in 199,900 Figures would be substantially higher if calculated for patients with febrile UTI There is considerable uncertainty in the relationship between childhood UTI and risk of ESRF based on the data currently available. Until further evidence is available clinicians will continue to debate the risk of UTI and ESRF and consensus opinion will continue to guide management. Round J, et al Acta Paediatr. 2012;101:278-282 3

Annals of Emergency Medicine 2013 May;61(5):559-65 Need to detect and treat early? Observational studies seeking predictors of scarring, most found no difference in scarring for patients among whom antibiotics were initiated less than 12 hours from fever onset versus up to 5 days from onset of fever; Doganis D et al Pediatrics. 2007;120(4):e922 e928; Lee YJ et al Urol. 2012;187:1032 1036; Fernández-Menéndez JM et al; Acta Paediatr. 2003;92:21 26 ;one did find association between scarring and antibiotics delayed after 4.5 day Oh et al Eur J Pediatr. 2012;171:565 570 Authors caution against drawing conclusions and did not condone waiting for 4 days before seeking treatment 4% prevalence of bacteremia found in one study of children 1 month to 24 months of age with fever and UTI (highest in younger age and longer duration of fever before treatment); Hoberman et al Pediatrics. 1999;104(1 pt 1):79-86 4

Occult UTI Well Appearing Infants 2-24 months of age Raising the Pre-test Probability for UTI in Febrile Infants 2-24 months Prevalence Varies by: Sex Race Degree of fever Circumcision status Presence of a possible source for fever. 5

Prevalence of UTI in Febrile Infants in the Emergency Department Hoberman et al J Pediatr, 1993 Shaw et al Pediatr, 1998 N % (95% CI) N % (95% CI) Overall 945 5.3 (3.9-6.7) 2411 3.3 (2.6-4.0) Sex Male Female 526 419 2.5 8.8 (1.1-3.8) (6.1-11.5) 942 1469 1.8 4.3 (1.0-2.6) (3.3-5.3) Race White African- American Other 533 392 20 6.6 3.6 5.0 (4.5-8.7) (1.7-5.4) (4.6-14.6) 291 2014 106 10.7 2.1 5.7 (7.1-14.3) (1.5-2.7) (1.3-10.1) Prevalence of UTI in Febrile Infants in the Emergency Department (cont d) Hoberman et al J Pediatr, 1993 Shaw et al Pediatr, 1998 N % (95% CI) N % (95% CI) Potential Source of Fever Yes No Fever in ED < 39 > 39 429 454 404 541 3.5 7.5 4.2 6.4 (1.8-5.2) (5.1-9.9) (2.2-7.2) (4.2-9.1) 1858 474 788 1623 2.7 5.9 2.2 3.9 (2.0-3.4) (3.8-8.0) (1.2-3.2) (3.0-4.8) 6

Prevalence of UTI in Febrile Infants in the ED (Boston)* Methods: Retrospective (N=11, 089) 30% of children < 2 yrs, > 38 C had UCx UTI Prevalence = 2.1% (95% CI: 2.0-2.1) Girls Boys Overall 2.9 1.5 White 5.0 2.2 Hispanic 2.1 1.4 Black 1.0 0.8 > 39 C 3.8 1.6 Female, < 6 mos, white, > 39 C 13% *Bachur and Harper. Arch Pediatr Adolesc Med, January, 2001 Prevalence of UTI in Febrile Infants meta-analysis Overall 7.0% Females 0-3mos 7.5 3-6mos 5.7 6-12mos 8.3 Males < 3 mos Circumcised 2.4 Uncirc ed 20.1 Race White 8.0 Black 4.7 Prevalence of UTI highest in females, uncircumcised males and whites. Shaikh PIDJ 2008; 27(4):302 7

Risk of UTI for Febrile White Young Girls in the Emergency Department Study Hoberman J Pediatr, 1993 Shaw Pediatr, 1998 Clinical Description White female; Temperature 39 C < 1 year of age White female; Temperature 38.5 C < 2 years of age Prevalence of UTI 16.9% 16.1% Hypothesis Relationship of Race and UTI Adherence of E. coli to urethral mucosa varies by blood group antigen type* Blood group antigen types vary by race *Jantausch BA et al. J Pediatr 1994;124:863-868 8

Predictive Model for Girls < 2 Years (N=1151; UTI=56) Predictors of UTI Adjusted Odds Ratio (95% CI s) Caucasian race 7.5 (4.2, 13,5) Age < 12 months 3.0 (1.5, 5.9) Temperature 39 C 2.6 (1.3, 5.4) No other potential source for fever Duration of fever 2 days 2.4 (1.3, 4.5) 2.0 (1.1, 3.6) Gorelick, M. H. and K. N. Shaw (2000). "Clinical decision rule to identify febrile young girls at risk for urinary tract infection." Arch Pediatr Adolesc Med 154(4): 386-90. ROC Curve of 5 Factor Predictive Model for UTI in Girls < 2 Years of Age @ CHOP Sensitivity AUC = 0.77 > 2 > 1 > 3 > 4 1-Specificity 9

Validation of the Decision Rule Identifying UTI in Febrile Young Girls + Retrospective, case-control study Pittsburgh s Children s Hospital Decision Rule Sensitivity FPR AUC > 3 factors (Pittsburgh) > 2 factors (Philadelphia) 88% 70% 0.72 95% 69% 0.77 +Gorelick et al. Pediatr Emerg Care, 2003 What about boys? A urine culture should be obtained: For boys < 12 months if: Adjusted Odds Ratio Not circumcised 9.7 No other potential source for fever on exam 4.0 < 6 months 3.2 Shaw et al: Pediatr, 1998 10

What prevalence or pre-test probability reaches the threshold for testing? At a UTI prevalence of 1-3% 67.5% of academicians and 45.7% of practitioners considered the yield sufficiently high to warrant urine culture. AAP Clinical Practice Guideline 2011 Annals of Emergency Medicine Editorial Response 2013 May;61(5):566-8. 11

Three Areas of Agreement (1) there is uncertainty about the relationship between childhood urinary tract infection and risk of renal scarring or end-stage renal failure according to the data currently available; (2) [p]ediatric urinary tract infection remains an important clinical entity, and attempts to identify and prevent sepsis and its sequelae, as in all infectious conditions, are critical ; (3) immediate screening of all infants who present to an ED for fever is not warranted according to current knowledge. Action Statement 2 Determine Likelihood of UTI If a clinician assesses a febrile infant with no apparent source for the fever as not being so ill as to require immediate antimicrobial therapy, then the clinician should assess the likelihood of UTI Action Statement 2a If the clinician determines the febrile infant to have a low likelihood of UTI, then clinical follow-up monitoring without testing is sufficient (evidence quality: A; strong recommendation). 12

Rational Approach Based on Evidence Screening Criteria Evidence More Information www.chop.edu/pathways Action Statement 2b : For febrile infants at risk, options for screening urine Option 1 is to obtain a urine specimen through catheterization, or SPA for culture and urinalysis Option 2 is to obtain a urine specimen through the most convenient means and to perform a urinalysis. If the urinalysis results suggest a UTI (positive LE or test nitrite test UA positive for leukocytes or bacteria), then a urine specimen should be obtained through catheterization or SPA and cultured; if urinalysis of fresh urine (<1 hour since void) is negative then it is reasonable to monitor the clinical course without initiating antimicrobial therapy, recognizing that negative UA/dipstick does not R/O UTI with certainty 13

CHOP UTI Screening Data Febrile Infants 2-24 months UTI Prevalence (using option 1) 1995 Universal Screening: 3 % 83% of eligible patients screened (no pathway or pre-test probability) 2012 Pathway Screening: 5% 73% of all febrile 2-24 month infants screened for UTI All by urethral catheritization Goal: Urinary Tract Infection Switching to Option 2 catheterizations in infants being evaluated for a UTI Rationale: Fever is a common emergency department (ED) complaint that may signify an occult bacterial infection, often requiring screening to rule out urinary tract infection (UTI). Catheterization has been the recommended way to screen for UTI in children that are not toilet trained. A retrospective review revealed that 73% of febrile patients were screened via catheterization, but 90% of them had both a negative screen and a negative culture. Target: Implement a new screening protocol using urine bags for the initial screen for infants 6 months to 24 months, with catheterizations used only when a screen was positive and needed to be sent for culture. Team Leads: Kathy Shaw, MD & Jane Lavelle, MD Team Members: Mercedes Blackstone, MD; Tricia Lopez, CRNP; Christine Roper, RN; Mary Kate Funari, RN; Catherine Botos; AllisonMak Improvement Advisor: Aileen Schast, PhD Data Analyst: Xianqun Luan, MS 14

Urinary Tract Infection CQI PDSA Cycles Project Timeline Project Start PDSA Cycles Project Moves to Sustain **Selected for two oral presentations at October s AAP meeting in San Diego** Screening Urine for UTI Using a Bag Spares many babies a painful procedure Does not delay care or increase ED LOS Over 1000 patients screened, only 330 cathed UTI Prevalence 4% Predictive Power Positive for + Screen = 50% 15

CHOP UTI Screening Procedure Febrile Infants 2-24 months Infants 2 to 6 months Obtain urine by catheterization for POC dipstick and culture (even if POC is negative) Do not hold urine in bladder higher rate of false negative POC disptick Higher rate of bacteremia; prevalence of UTI Infants 6 months to 24 months Place Urine bag upon arrival to Room Do POC dipstick if Positive Screening Score If POC Urine Dipstick is positive cath for CX POC Urine Testing 16

Comparison of Screening Tests Definition of + POC Screen Test Percentage (95% CI) Sensitivity Specificity PV Gram stain: Single organism Dipstick:+3 LE or Nitrite Dipstick + U/A: >5 WBC and BACT/HPF 79 (67-88) 98 (97-98) 49 (39-59) 73 (62-81) 99 (98-99) 61 (52-70) 73 (62-81) 98 (98-99) 57 (47-65) Enhanced U/A: >10 WBC/mm 3 and Gram stain PV Ө > 99% for all tests 75 (61-86) 99 (99-100) 80 (66-90) Action Statement 1: Cultures obtained Cath or SPA only If a clinician decides that a febrile infant with no apparent source for the fever requires antimicrobial therapy to be administered because of ill appearance or another pressing reason, the clinician should ensure that a urine specimen is obtained for both culture and urinalysis before an antimicrobial agent is administered; The specimen needs to be obtained through catheterization or SPA, because the diagnosis of UTI cannot be established reliably through culture of urine collected in a bag (evidence quality: A; strong recommendation). 17

Percent Higher Rates of Urine Culture Contamination for Bag Specimens 80 Negative 60 Positive Contaminant 40 20 0 Overall N=7584 Cathed Specimens Bag Specimens Al-Orifi et al. J Pediatr, August, 2000 Bag Vs. Cath Specimens* Adverse Outcome Adjusted Odds Ratio (95% CI) Contamination* 13.3 (11.3, 15.6) Unnecessary recall* 4.9 (2.3, 10.5) Delayed Dx & Rx* (no cases for cathed specimen) Unnecessary Rx* 4.8 (1.8, 12.4) Prolonged treatment 4.1 (1.4, 12.1) Unnecessary radiologic w/u 15.6 (2.1, 116.8) Unnecessary admission 12.4 (1.6, 95.5) Al-Orifi et al. J Pediatr, August, 2000 18

Action Statement 3 Definition of UTI To establish the diagnosis of UTI, clinicians should require both urinalysis results that suggest infection (pyuria and/or bacteriuria) and the presence of at least 50 000 colonyforming units (CFUs) per ml of a uropathogen cultured from a urine specimen obtained through catheterization or SPA (evidence quality: C; recommendation). Treatment for Febrile UTI Empiric Treatment Urine Dipstick: Moderate (2+) LE or + Nitrite UA: >5WBC/hpf and bacteria CHECK CX: Half will be negative (PNP F/U) Fever and UTI = Pyelonephritis (consider admission <6 months) 2/3 of children with febrile UTI show kidney involvement on renal scans May be treated with oral antibiotics (2 vs 6 months?) Negative cultures at 24 hours, without increased reinfectons with IV cefotaxime vs oral cefixime Hoberman Peds 1999;104(1):79 19

Action Statement 4 : Treatment Action Statement 4a When initiating treatment, the clinician should base the choice of route of administration on practical considerations. Initiating treatment orally or parenterally is equally efficacious. The clinician should base the choice of agent on local antimicrobial sensitivity patterns (if available) and should adjust the choice according to sensitivity testing of the isolated uropathogen (evidence quality: A; strong recommendation). Action Statement 4b The clinician should choose 7 to 14 days as the duration of antimicrobial therapy (evidence quality: B; recommendation). Recommended Antitiotics 20

Antibiotic Sensitivities to E Coli at CHOP Ampicillin 51 Amp/Sulbactam 65 Cefazolin 90 Cefepime 99 Cefoxitin 96 Ceftazidime 98 Ceftriaxone 98 Ciprofloxacin 93 Gentamicin 94 Imipenem 100 Meropenem 100 Nitrofurantoin 96 Pip/Tazobacta 97 Tobramyci 95 Trimethoprim/Sulf 74 Urine CX + Do I have to have an Ultrasound and VCUG? 21

After the ED: Counseling the Parent RBUS Yes; VCUG probably not 5. Febrile infants with UTIs should undergo renal and bladder ultrasonography (RBUS) (evidence quality: C; recommendation). 6a. VCUG should not be performed routinely after the first febrile UTI; VCUG is indicated if RBUS reveals hydronephrosis, scarring, or other findings that would suggest either high-grade VUR or obstructive uropathy, as well as in other atypical or complex clinical circumstances (evidence quality B; recommendation). 6b. Further evaluation should be conducted if there is a recurrence of febrile UTI (evidence quality: X; recommendation). 7. After confirmation of UTI, the clinician should instruct parents or guardians to seek prompt medical evaluation (ideally within 48 hours) for future febrile illnesses, to ensure that recurrent infections can be detected and treated promptly (evidence quality: C; recommendation). Case #1 15 Month Old White Female 3 day history of fever: appetite, runny nose Exam: 40ºC HR 125 RR 30 BP 100/50 Sick, not toxic, bilateral serous OM Positive rhinorrhea Urine score = 3 (fever duration, temp, race) Urine bag placed upon arrival to room Urine dipstick results: nitrite, large LE Cathed for urine Cx (>100,000CFU E Coli) Treated with Keflex; PCP arranges RBUS in 4-6 weeks 22

Case #2 8 Month Old Hispanic Male 3 day history: Fever, irritability, loose stools Exam: 38.9ºC HR 140 RR 32 BP 96/53 Crying, easily consolable Abdomen - soft, non-tender GU - uncircumcised Urine score = 2 (uncircumcised, no source) Urine Bag place in the room Urine dipstick results: nitrite, moderate LE Cathed for Cx (>100.000 CFU Proteus) Treated with Keflex; PCP arranges RBUS in 4-6 weeks Case #3 4 Month Old African-American Female 1 day history: Fever, irritability Exam: 39.6ºC HR 150 RR 36 BP 90/50 Social smile, non-toxic No source of fever on exam Urine score = 3 (age, temp, no source) Cathed for Urine POC dipstick plus CX Urine dipstick results: nitrite, large LE Admited for IV Ampicillin and Gentamycin UCx + (>100,000 Ecoli) RBUS Neg; home on Keflex at 36 hrs 23

UTI Propylaxis - Controversial 24

The RIVUR study Randomized Intervention for Children with VesicoUreteral Reflux RIVUR STUDY 25