The major pathogens causing acute otitis media (AOM) are Streptococcus pneumoniae and Haemophilus influenzae, with Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus less frequently isolated. The same organisms and Staphylococcus epidermidis are found in chronic otitis media with effusion. In chronic suppurative otitis media, Pseudomonas aeruginosa and S aureus are most frequently found. Antimicrobial agents found to be most effective in treating AOM are amoxicillin, trimethoprimsulfamethoxazole, erythromycin-sulfisoxazole, amoxicillin-clavulanate, and cefaclor. Cefuroxime axetil and cefixime are alternatives for which there are less data. Currently, about 20% of AOM cases are caused by beta-lactamase-producing strains (usually H influenzae or M catarrhalis) that are resistant to amoxicillin, thus favoring the use of the other agents listed. Concentrations of antibiotics in middle ear infections range from 10% to 76% of peak serum levels for the listed agents and are higher in AOM than in chronic otitis media with effusion, emphasizing the importance of adequate dosing for successful treatment.