Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the influence of beta-lactamase production on cefditoren activity, 1,170 H. influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of cefditoren (MIC(90,) 0.015 microg/mL) was similar to that of ceftriaxone (MIC(90,) < or = 0.015 microg/mL) and levofloxacin (MIC(90,) 0.015 microg/mL), and its MIC distribution was unaffected by beta-lactamase production. In comparison, the beta-lactamase status of M. catarrhalis affected the potency of all beta-lactams tested, including cefditoren, as well as trimethoprim-sulfamethoxazole. However, regardless of the presence of beta-lactamase, cefditoren demonstrated potent activity, as concentrations of 0.5 and 1 microg/mL inhibited 93.1 and 100% of M. catarrhalis isolates, respectively. We conclude that cefditoren is highly active in vitro against beta-lactamase-positive H. influenzae and M. catarrhalis.