Affinity of ceftobiprole for penicillin-binding protein 2b in Streptococcus pneumoniae strains with various susceptibilities to penicillin.
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.
Davies
Todd A
TA
Johnson & Johnson Pharmaceutical Research & Development, LLC, Room B215, 1000 Route 202, Raritan, NJ 08869, USA. tdavies1@its.jnj.com
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Wenping
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Bush
Karen
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Flamm
Robert K
RK
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*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; C443755:ceftobiprole; D002443:Ceftriaxone