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Antimicrobial Agents and Chemotherapy, June 2006, p. 2050-2057, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00044-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Activities of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis

Tatiana Bogdanovich,1 Catherine Clark,1 Lois Ednie,1 Gengrong Lin,1 Kathy Smith,1 Stuart Shapiro,2 and Peter C. Appelbaum1*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,1 Basilea Pharmaceutica AG, Basel, Switzerland2

Received 11 January 2006/ Accepted 20 March 2006

Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 µg/ml and 8.0 µg/ml for 321 clinical isolates of Haemophilus influenzae and between ≤0.004 µg/ml and 1.0 µg/ml for 49 clinical isolates of Moraxella catarrhalis. Ceftobiprole MIC50 and MIC90 values for H. influenzae were 0.06 µg/ml and 0.25 µg/ml for ß-lactamase-positive strains (n = 262), 0.03 µg/ml and 0.25 µg/ml for ß-lactamase-negative strains (n = 40), and 0.5 µg/ml and 2.0 µg/ml for ß-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprole MIC50 and MIC90 values for ß-lactamase-positive M. catarrhalis strains (n = 40) were 0.12 µg/ml and 0.5 µg/ml, respectively, whereas the ceftobiprole MIC range for ß-lactamase-negative M. catarrhalis strains (n = 9) was ≤0.004 to 0.03 µg/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 telithromycin of 2 µg/ml and 4 µg/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC90 values of 0.12 µg/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2x 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.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, 500 University Drive, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2050-2057, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00044-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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