Open AccessActivities of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis
Author(s) -
Tatiana Bogdanovich,
Catherine L. Clark,
Lois M. Ednie,
Gengrong Lin,
Kevin M. Smith,
Stuart Shapiro,
Peter C. Appelbaum
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00044-06
Subject(s) - moraxella catarrhalis , haemophilus influenzae , cephalosporin , moraxella (branhamella) catarrhalis , microbiology and biotechnology , broad spectrum , antibacterial agent , medicine , antibiotics , chemistry , biology , combinatorial chemistry
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 ofHaemophilus influenzae and between ≤0.004 μg/ml and 1.0 μg/ml for 49 clinical isolates ofMoraxella catarrhalis . Ceftobiprole MIC50 and MIC90 values forH. influenzae were 0.06 μg/ml and 0.25 μg/ml for β-lactamase-positive strains (n = 262), 0.03 μg/ml and 0.25 μg/ml for β-lactamase-negative strains (n = 40), and 0.5 μg/ml and 2.0 μg/ml for β-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprole MIC50 and MIC90 values for β-lactamase-positiveM. catarrhalis strains (n = 40) were 0.12 μg/ml and 0.5 μg/ml, respectively, whereas the ceftobiprole MIC range for β-lactamase-negativeM. 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 againstH. influenzae , with MIC90 values of azithromycin and telithromycin of 2 μg/ml and 4 μg/ml, respectively. Except for selected quinolone-nonsusceptibleH. 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 2× MIC by 24 h against all 10H. influenzae strains surveyed. Only modest increases in MICs were found forH. influenzae orM. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency ofH. influenzae orM. catarrhalis clones with elevated ceftobiprole MICs is quite low.