Objectives. To determine the bacteriologic and clinical efficacy of high do
se amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial path
ogens causing acute otitis media (AOM), including penicillin-resistant Stre
ptococcus pneumoniae (PRSP).
Methods. In this open label multicenter study, 521 infants and children wit
h AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated
with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 d
ays. Bilateral otitis media, previous episodes of AOM, antibiotic treatment
within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2
and 38.2% of the children, respectively. Tympanocentesis was performed befo
re the first dose and repeated on Days 4 to 6 for all children with S. pneu
moniae at 22 centers and for all children with any pathogen at 3 centers. C
linical response was assessed at end of therapy.
Results. Pathogens were isolated from 355 (68%) of 521 enrolled children; 1
80 children underwent repeat tympanocentesis and were bacteriologically eva
luable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacterio
logically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32)
and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bac
teriologically evaluable children. Overall 122 (98%) of 125 isolates of S.
pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicil
lin MICs 2 to 4 mug/ml). Seventy-eight (94%) of 83 isolates of H. influenza
e were eradicated. Symptoms and otoscopic signs of acute inflammation were
completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinic
ally evaluable children with bacteriologically documented AOM.
Conclusions. On the basis of bacteriologic outcome on Days 4 to 6 and clini
cal outcome on Days 12 to 15, we found that high dose amoxicillin/clavulana
te (90/6.4 mg/kg/day) was highly efficacious in children with AOM, includin
g those most likely to fail treatment, namely children < 24 months of age a
nd those with infections caused by PRSP.