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
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.
No differences in demographics, clinical and laboratory characteristics
between treatment groups.
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.
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.
Pathogens included predominately E.coli (298 children)
and several others.
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.
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.
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).
Mean costs 2-fold higher for children receiving IV versus