Pediatric urinary tract infection

1. Pediatric urinary tract infection Scott Weissman, MD Fellows’ orientation 8 July 2009

2. Presentation of UTI in children • Newborn (1-30 d) • Non-specific signs/symptoms • Considered as sepsis; neonates do not localize • Infant/toddler (1 mo-4 yr) • Fever • Abdominal pain/vomiting/diarrhea • (Pre)school-age/adolescent (4 yr-) • Like adult presentation • Dysuria/frequency

3. Case presentation • 10 d/o M p/w poor feeding, grunting, T 103.6 • Taken to community ER, lethargic; w/u performed • Txfer to CHRMC, where septic, in DIC • Rx: fluid resuscitation, FFP, platelets, empiric amp/cefotax • Responded well to interventions • Urine culture negative, blood culture (+) GNR • LP traumatic, unsuccessful x1; later repeat successful but xanthochromic, elev WBC, RBC and protein

4. Case presentation (cont.) • Previous medical history • Prenatal ultrasound (+) B hydronephrosis • No oligohydramnios, but labor induced @ 37 wk • Good urinary output, stream; o/w appeared well • Postnatal RUS (+) mod. hydronephrosis • D/C home DOL #2 • Cr 0.2 on DOL #7 at well-child check • Hospital course • Cr 0.8 • Due to daily fevers, repeat RUS on HD #3 • (+) multiple hypoechoic lesions in R renal parenchyma • ID consultation re management of nephronia +/- ?CNS

5. Issues in pediatric UTI • Antenatal ultrasound dx of hydronephrosis • Cost effectiveness of RUS at first UTI • Septic complication of congenital abnormality • Early-onset vs. late-onset E. coli infection • GI txlocation vs. GI colonization/ascending UTI • Length of therapy per presentation

6. Diagnosis • Bagged sample • Easy, atraumatic • Perineal contamination - useful only if negative • Catheterized sample • More difficult, may be traumatic, nurse can do • Collection systems don’t allow discard first cc’s • Bladder tap sample • Must be performed by physician • Minimal complications, lowest risk of contamination

7. aac(3)-II TEM-1 OXA-1 tetA aac(6’)-Ib CTX-M-15 Etiologic agents • Escherichia coli • Concerns for increasing prevalence of ESBL- producing strains; eg, ST131 (O25:H4) Multidrug resistance region of plasmid pC15-1a, carried by widely-disseminated E. coli clone ST131.

8. Additional etiologic agents • Urology patients: congenital abnormalities, post-surgical • Pseudomonas aeruginosa • Klebsiella species: chromosomal ESBL (SHV type), plasmid ESBL • SPICEM organisms (Serratia, Providencia, indole-positive Proteus, Citrobacter, Enterobacter, Morganella) • Produce chromosomal AmpC beta-lactamases that confer resistance to most extended spectrum BLs • Nosocomial infections in Foley catheterized patients • Candida species • Community-acquired UTI in older adolescents • Coagulase-negative staph (S. saprophyticus), as for adults

9. Treatment • Antibiotic selection • Newborns: Amp+gent empirically, then tailored • In presented case, gent initially withheld d/t Cr, but upon resolution, given x1 wk for renal parenchymal penetration • Older patients: ceftriaxone, if ill; TMP/SMX, nitro, ?cipro if not ill • Route of therapy • Parenteral - for neonates, and as initial rx for complicated UTI • Oral - for uncomplicated UTI, and for stabilized complicated UTI • Cefixime PO comparable to ceftriaxone for pts 2 mo - 2 yr • Must be vigilant re compliance, vomiting • Length of therapy • Newborn UTI: 14 d (as for GNR sepsis) • Pyelonephritis: 10-14 d • Cystitis: 3-7 d, per age

10. Fluoroquinolones in pediatrics • Toxicity concerns re damage to cartilage in multiple juvenile animal models • Record of safety in Europe, in cystic fibrosis • Clinical indications • UTI caused by P. aeruginosa or 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)

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

12. Evaluation of pediatric UTI • Per AAP Guidelines, for all children 2 mo - 2 yr with first UTI, evaluation recommended • Renal ultrasound, to be done early in UTI • To look for abscess or obstruction • To look for anatomic abnormalities • Vesicocystoureterogram (VCUG) • To look for VUR, dysfunctional voiding, subtle anatomic defects • May be done early or late • If VUR found, prophylactic antibiotics given

13. Vesicoureteral reflux (VUR)

14. Antibiotic prophylaxis in VUR • Pts w/documented VUR of any grade have been rx’d prophylactically • TMP/SMX, TMP only, SMX only • Nitrofurantoin • Based on assumptions (and some data) • Chronic prophylactic antibiotics reduce risk of UTI • Prevention of UTI will prevent renal scarring

15. 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. America, data coordinated at UNC • Increasing use of cystoscopic Deflux (hyaluronic acid gel) injection at vesicoureteral junction

16. References 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 Urol 179:405-7. 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.