Activities of ceftobiprole, a novel broad-spectrum cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis

Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cepbem currently in phase III clinical trials, had MICs between 0.008 mu g/ml and 8.0 mu g/ml for 321 clinical isolates of Haemophilus influenzae and between <= 0.004 mu g/ml and 1.0 mu g/ml for 49 clinical isolates of Moraxella catarrhalis. Ceftobiprole MIC50 and MIC90 values for H. influenzae were 0.06 mu g/ml and 0.25 mu g/ml for P-lactamase-positive strains (n = 262), 0.03 mu g/ml and 0.25 mu g/ml for beta-lactamase-negative strains (n = 40), and 0.5 mu g/ml and 2.0 mu g/ml for beta-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprolle MIC50 and MIC90 values for beta-lactamase-positive M. catarrhalis strains (n = 40) were 0.12 mu g/ml and 0.5 mu g/ml, respectively, whereas the ceftobiprole MIC range for beta-lactamase-negative M. catarrhalis strains (n = 9) was <= 0.004 to 0.03 mu g/ml. Ceftriaxone MICs usually were generally at least twofold lower than those of ceftobiprole, whereas amoxicillin-clavulanate MICs usually were higher than those of ceftobiprole. Azithromycin and telithromycin had unimodal MIC distributions against H. influenzae, with MIC90 values of azithromycin and tellithromycin of 2 mu g/ml and 4 mu g/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC,0 values of 0.12 mu g/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2 X MIC by 24 h against all 10 H. influenzae strains surveyed. Only modest increases in MICs were found for H. influenzae or M. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency of H. influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low.