University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Is oral therapy (i.e. cefixime) a safe and effective treatment for children with fever and UTI?

Clinical Bottom Lines

1. Oral cefixime and IV cefotaxime have equivalent efficacy and safety for treatment of UTI in young children with fever. 
2. Use of cefixime may decrease health care expenditures.

Summary of Key Evidence

1. Multicenter, randomized clinical trial – 306 children age 1 to 24 months with fever and UTI (T > 38.3 at presentation or within 24 hours & suspected UTI based on pyuria and bacteriuria.  Final eligibility was positive urine cx, > 50,000 cfu/ml with single pathogen from cath specimen).  Subjects were randomized based on age (1-12 months, 13-24 months) and duration of fever (<48 hrs or >48 hrs).¹
2. Children were excluded from study if negative urine clx, hypersensitivity to cephalosporins, GPC on stained urine, h/o UTI or abnormality of urinary tract, unequivocal alternative source of fever, systemic antibiotics within 48 hrs, or underlying chronic disease.  Eligible children judged to be severely ill (SBP < 60, cap refill > 3 sec) were excluded from randomization. 
3. No differences in demographics, clinical and laboratory characteristics between treatment groups. 
4. Patients received either oral cefixime (8 mg/kg/d) for 14 days (double dose on day 1) or IV cefotaxime for 3 days (or until afebrile x24 hrs) followed by cefixime for 11 days.  After 14 day course, cefixime (4 mg/kg/d) given prophylactically for 2 weeks until VCUG.  Exceptions were 1)  children between 4-8 wks of age assigned to oral treatment were admitted to hospital initially to monitor progress, then discharged to finish cefixime.  2) Children vomiting were hydrated then discharged to complete course after initial dose. 
5. DMSA scans done at study entry and again 6 months later.  Renal U/S done initially and VCUG done 4-5 wks out.  No statistically significant differences between treatment groups.  Acute phase reactants higher in children with evidence of acute pyelonephritis on initial DMSA scan. 
6. Pathogens included predominately E.coli (298 children) and several others. 
7. Compliance assessed at 2 week visit or at time of VCUG by testing urine for cefixime.  Detectable in 85% of 186 children for whom a urine specimen was available – no difference between groups. 
8. Short term outcomes 
   a) sterilization of urine – occurred in all children within 24 hrs.
   b) defervescence – within 25 hrs for children treated orally, 24 hrs for children treated with IV. 
   c) bacteremia was documented in 13 children – 5 received oral therapy and 8 received IV therapy.  Clinically indistinguishable but tended to be younger, longer duration of fever, higher acute phase reactants. 
9. Long term morbidity 
   a) incidence of reinfection – 4.6% of children treated orally and 7.2% of children treated with IV.  Children were followed for 6 months and urine cultures obtained at 3 and 6 months and whenever child had fever.
   b) incidence of renal scarring documented at 6 months by DMSA scan – about 8% in both groups.  Only the degree of VUR was associated significantly w/ a higher incidence of renal scarring (regardless of mode of therapy). 
10. Mean costs 2-fold higher for children receiving IV versus oral therapy.

Additional Comments

• List any pertinent issues in the critical appraisal
• List any key biological mechanisms at issue
• List key elements of the cost or other consequences of executing the bottom line (such as side-effects or toxicity)

Citation

1. Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, Kearney DH, Reynolds EA, Ruley J, and Janosky JE.  Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 104(1): 79-86, 1999.

CAT Author: Amy Mikhail, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: August 9, 1999