High dose (70 to 90 mg/kg/day) amoxicillin
is recommended as first line therapy of acute otitis media
(AOM) in geographic areas where drug-resistant Streptococcus pneumoniae
is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin
treatment for AOM is limited.
To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin
as first line therapy in AOM.
In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin
(80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse
occurred. Bacteriologic failure
was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 ± 2. Susceptibility to penicillin and amoxicillin
was measured by E-test.
Sixty-five organisms were recovered at enrollment:Haemophilus influenzae
(38), Streptococcus pneumoniae
(24), Streptococcus pyogenes
(2) and Moraxella catarrhalis
(1). Eighteen (75%) S. pneumoniae
were nonsusceptible to penicillin (MIC > 0.1 μg/ml). All 24 S. pneumoniae
isolates had amoxicillin
MIC ≤ 2.0 μg/ml. Thirteen (34%) of the 38 H. influenzae
were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae,
21 of 25 (84%) beta-lactamase-negative H. influenzae,
8 of 13 (62%) beta-lactamase-positive H. influenzae
, 2 of 2 S. pyogenes
and 1 of 1 M. catarrhalis.
Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae
; 1 beta-lactamase-negative H. influenzae
; 2 S. pneumoniae
; and 1 M. catarrhalis
. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae
. Three (33%) of the 9 patients with bacteriologic failure
(2 beta-lactamase-positive H. influenzae
, 1 S. pneumoniae
) failed also clinically on Days 4 to 6.
The predominant pathogens isolated from children with AOM failing high dose amoxicillin
therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin
is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.