title: Affinity of ceftobiprole for penicillin-binding protein 2b in Streptococcus pneumoniae strains with various susceptibilities to penicillin.
abstract: Wild-type penicillin-binding protein (PBP) 2b from penicillin-susceptible Streptococcus pneumoniae had high affinity for ceftobiprole and penicillin (50% inhibitory concentrations [IC(50)s] of ≤0.15 μg/ml) but not ceftriaxone (IC(50) of >8 μg/ml). In clinical isolates, ceftobiprole and PBP 2b affinities were reduced 15- to 30-fold with a Thr-446-Ala substitution and further still with an additional Ala-619-Gly PBP 2b substitution. Ceftobiprole remained active (MICs of ≤1 μg/ml) against all strains tested and behaved more like penicillin than ceftriaxone with respect to PBP 2b binding.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, Room B215, 1000 Route 202, Raritan, NJ 08869, USA. tdavies1@its.jnj.com
authors.forename: Todd A
authors.initials: TA
authors.lastname: Davies
authors.forename: Wenping
authors.initials: W
authors.lastname: He
authors.forename: Karen
authors.initials: K
authors.lastname: Bush
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D002443:Ceftriaxone / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000378:metabolism*; D010406:Penicillins / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; C443755:ceftobiprole; D002443:Ceftriaxone