Abstract Switch therapy, the switch from a parenteral to an oral antimicrobial agent, has been used successfully in the treatment of many serious infections. The purpose of this study was to determine whether cefixime, a third-generation oral cephalosporin, could be used in switch therapy from ceftriaxone or cefotaxime. The in vitro activity and resulting concordance of susceptibility test results of these agents was determined for 2284 aerobic bacterial isolates. For isolates of penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis, there was 100% concordance in susceptibility between cefixime, cefotaxime, and ceftriaxone. However, in isolates of Enterobacteriaceae and S pneumoniae with reduced susceptibility to penicillin, > 5% of isolates resistant to cefixime remained susceptible to ceftriaxone and cefotaxime. Therefore, results of this study suggest that for respiratory pathogens other than S pneumoniae with reduced susceptibility to penicillin, cefixime can be used as a switch agent from cefotaxime or ceftriaxone. In isolates of Enterobacteriaceae and in regions where S pneumoniae with reduced susceptibility to penicillin is prevalent, in vitro susceptibility testing should be done before switch therapy with cefixime is used.