--The present results suggest that, as in children, amoxicillin would be an appropriate first-line agent for empiric therapy of acute otitis media in adults. Antimicrobials inactive against H influenzae (eg, penicillin V, cephalexin, erythromycin, or tetracyclines) are not appropriate for initial therapy. Antimicrobials with efficacy against organisms producing beta-lactamase, such as cefuroxime axetil, which was used to treat the study patients, do not appear to be required for routine initial therapy in adults. However, they would be appropriate when an organism producing beta-lactamase is isolated from the middle ear or when a patient fails to improve rapidly on amoxicillin therapy.