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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology
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Ceftriaxone / metabolism
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Ceftriaxone / pharmacology
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Cephalosporins / metabolism*
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Cephalosporins / pharmacology*
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Inhibitory Concentration 50
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Microbial Sensitivity Tests
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Penicillin-Binding Proteins / metabolism*
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Penicillins / metabolism*
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Penicillins / pharmacology*
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Protein Binding
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Streptococcus pneumoniae / drug effects*
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Streptococcus pneumoniae / metabolism*
Substances
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Anti-Bacterial Agents
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Cephalosporins
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Penicillin-Binding Proteins
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Penicillins
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ceftobiprole
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Ceftriaxone