Pediatric urinary tract infection

1. Pediatric urinary tract infection Scott Weissman, MD Fellows’ orientation 7 July 2010

7. Pediatric UTI by age • Non-toilet-trained children (NTTC) • Newborn/infants (up to 60 d) • Present with non-specific signs/symptoms • Managed by ‘rule out sepsis’ guideline • Toddlers (up to 2-3 yr) • Unable to express themselves well • Present with fever, abd pain, vomiting/diarrhea • Toilet-trained children (TTC) • Pre/school-age (up to 12 yr) • Can describe/localize sx • Present like adults: dysuria, frequency • Adolescent (13 yr and older) • Potentially sexually active

8. New recommendations: Diagnosis • Diagnose UTI in NTTC via high quality urine specimen (ie, not a bag) • Catheter • Suprapubic tap • In adolescents, document external GU exam and test for GC/Chlamydia • Nucleic acid amplification tests; send-out to UW • NOT clean catch or midstream - collect first 20 cc

9. New Recommendations: Empiric Rx • When to start empiric therapy • In NTTC – for clinical suspicion • In TTC – for clinical findings plus (+) UA/urine dip/microscopy • What to start • Newborns (0-30 d) • IV amp + gent • Infants (over 30 d): • IV ceftriaxoneif admit; IV amp + gent if suspect E-coccus • Infants (30-60 d) not admitted: • IM ceftriaxone • Older children (over 60 d): • PO cephalexin; if CS allergy, PO Bactrim • IM ceftriaxone

10. New Recommendations: Empiric Rx • Length of therapy • Newborn (0-30 d): 7 d IV followed by 7 d PO • Infant (31-60 d): IV until afebrile x 24 h and BCx (-) x 36 h, followed by PO to complete 14 d • Adolescents: 3 d PO

11. Antibiotic Resistance

12. PBLR Enterobacteriaceae Seattle Children’s 1999-2009 # isolates Year

13. chromosome plasmid active ampC inactive ampC AmpC enzymes are encoded on chromosomes and plasmids SPICEM Serratia, Providencia, indole-positive Proteus, Citrobacter, Enterobacter, Morganella E. coli Salmonella

14. Etiologic agents and Resistance

15. aac(3)-II TEM-1 OXA-1 tetA aac(6’)-Ib CTX-M-15 Emerging Resistance • Escherichia coli • Class A enzyme CTX-M-15 associated with emerging clone ST 131 (serotype O25:H4) • Class C enzyme CMY-2 associated with multiple clones (and multiple species, e.g., Salmonella Typhimurium) Multidrug resistance region of plasmid pC15-1a, carried by widely-disseminated E. coli clone ST131.

16. Ciprofloxacin • Toxicity concerns re damage to cartilage in multiple juvenile animal models • Record of safety in Europe, in cystic fibrosis • Per AAP, increasing resistance is a growing concern • Clinical indications • UTI caused by P. aeruginosaor other multidrug-resistant gram-negative bacteria (per AAP) • Complicated E. coli UTI and pyelonephritis attributable to E. coli in pts 1-17 yrs of age (per FDA) • Patient/family counseling • “If use of an FQ is recommended for a patient younger than 18 y/o, the risks and benefits should be explained to the pts and parents” (AAP Red Book, 2006)

17. Fosfomycin • Bactericidal PO antibiotic with one-time dosing that inhibits bacterial cell wall synthesis • Inactivates pyruvyl transferase – first committed step in cell wall synthesis • High urinary levels > 48 h • 90% of SCH ESBL-producing E. coli susceptible • Approved for >12 yr • Powder form, comes in sachet, dissolved in water • Not on SCH formulary but available in community • Adverse reactions: headache, diarrhea, nausea, vaginitis

18. Cefixime • PO third-generation cephalosporin with once-daily dosing (dose amount doubled on day one) • Not for use in infants less than 3 months of age • Suspension contain sodium benzoate (metabolite of benzyl alcohol) • Large amounts of benzyl alcohol associated with fatal toxicity in newborns: ‘gasping syndrome’ • Metabolic acidosis, resp distress, gasping • CNS dysfunction (sz, ICH) • Hypotension, cardiovascular collapse • Benzoate displaces bilirubin from protein

19. New Recommendations: Imaging • Paradigm shift: Reduction in use of VCUG for initial imaging in children with first-time UTI • Infants and non-toilet-trained children • Renal ultrasound OR high-quality 3rd trimester US read as normal • VCUG only if atypical UTI - one of the following: • Seriously ill • Poor urine flow • Abdominal or bladder mass • Elevated creatinine • Septicemia • Failure to respond to appropriate rx within 48 h • Infection caused by organism other than E. coli • DMSA scan 12 months after atypical UTI

20. New Recommendations: Imaging • Toilet-trained children and adolescents • Renal ultrasound for boys with first UTI and for girls with atypical UTI • If VUR found, prophylactic antibiotics given

21. Underlying pathophysiology • Vesicoureteral reflux (VUR) • Up to 35% of children w/UTI under age 12 • Highest in 1 y/o (50%) • Posterior urethral valves (boys) • May be missed at birth • Ask parents about voiding stream • Dysfunctional voiding (girls) • Recurrent cystitis common • Voiding history is useful

22. Antibiotic prophylaxis in VUR • Historically, pts w/documented VUR of any grade have been rx’d prophylactically • TMP/SMX, TMP only, SMX only • Nitrofurantoin • Based on data from poorly-controlled studies and biological assumptions • Chronic prophylactic abx reduce risk of UTI • Prevention of UTI will prevent renal scarring

23. Antibiotic prophylaxis in VUR • Cochrane Review finds significant lack in evidence supporting these assumptions, need for methodologically-sound studies (see Williams et al) • RIVUR (Randomized Intervention for children with VesicoUreteral Reflux) study announced 2/08 • Multicenter, double-blind, randomized, placebo-controlled trial, to enroll 600 children 2-72 mos with grades I-IV VUR, to receive TMP/SMX or placebo • Collaboration of 15 clinical trial centers throughout N.A., data coordinated at UNC • Increasing use of cystoscopic Deflux (hyaluronic acid gel) injection at vesicoureteral junction

24. References Committee on Infectious Diseases (2006) Pediatrics 118:1287-1292. Committee on Quality Improvement, Subcommittee on Urinary Tract Infection (1999) Pediatrics 103:843-52. Cooper CS et al (2000) J Urol 163:269-73. DeMuri GP & ER Wald (2008) PIDJ 27:553-4. Garin EH et al (2006) Pediatrics 117:626-32. Greenfield SP et al (2008) J Urol179:405-7. Lavollay M et al (2006) AAC 50:2433-8. Reddy PP (1997) Pediatrics 100:555-6. Robicsek A et al (2006) Nat Med 12:83-8. Williams G et al (2006) Cochrane Database Syst Rev 3:CD001534.