Amoxicillin/clavulanic acid (
Augmentin),
Augmentin ES-600 is a well established, orally administered combination of
amoxicillin (a semisynthetic
antibacterial agent) and
clavulanic acid (a
beta-lactamase inhibitor).
Amoxicillin/clavulanic acid shows good activity against the main pathogens associated with acute
otitis media (AOM), including
penicillin-susceptible and -intermediate strains of Streptococcus pneumoniae, and
beta-lactamase producing strains of Haemophilus influenzae and Moraxella catarrhalis. It has moderate activity against
penicillin-resistant S. pneumoniae; a high-dose formulation has been developed with the aim of providing better coverage for
penicillin-resistant strains.
Amoxicillin/clavulanic acid (conventional formulations, mostly 40/10 mg/kg/day in three divided doses) produced clinical response rates similar to those of oral
cephalosporin comparators and similar to or significantly greater than those for intramuscular
ceftriaxone in randomised trials in paediatric patients with AOM (mean age approximately 2 to 5 years). Clinical response rates were generally similar for
amoxicillin/clavulanic acid and
macrolide comparators (mean patient age approximately 1 to 6 years), although significantly better clinical and bacteriological responses were seen versus
azithromycin in one randomised trial (mean patient age approximately 1 year). The high-dose formulation of
amoxicillin/clavulanic acid (90/6.4 mg/kg/day in two divided doses) eradicated a high proportion of
penicillin-resistant S. pneumoniae (
penicillin MICs 2 or 4 mg/L) in a large noncomparative trial in children with AOM (upper limit of the US indication for S. pneumoniae is 2 mg/L).
Amoxicillin/clavulanic acid is generally well tolerated. A low total incidence of adverse events (3.6%) and no serious events were reported from a large paediatric postmarketing study. The most frequently reported adverse events in children are mild gastrointestinal disturbances. Diarrhoea is generally less frequent with twice-daily than with three-times-daily treatment. The new high-dose formulation showed similar tolerability to a conventional twice-daily formulation (45/6.4 mg/kg/day) in a well controlled trial.
CONCLUSIONS:
Amoxicillin/clavulanic acid is a well established broad-spectrum antibacterial treatment which is effective and well tolerated in the treatment of AOM in paediatric patients. The high-dose combination should prove valuable in treating AOM caused by
penicillin-intermediate and -resistant S. pneumoniae (approved in the US for
penicillin MIC < or =2 mg/L). Based on recent recommendations and the available data, high-dose
amoxicillin/clavulanic acid can be considered a treatment of choice for recurrent or persistent paediatric AOM (after failure of
amoxicillin alone) where involvement of resistant pathogens is suspected.