Affinity of Ceftobiprole for Penicillin-Binding Protein 2b in Streptococcus pneumoniae Strains with Various Susceptibilities to Penicillin {triangledown}

Wild-type penicillin-binding protein (PBP) 2b from penicillin-susceptible Streptococcus pneumoniae had high affinity for ceftobiprole and penicillin (50% inhibitory concentrations [IC₅₀s] of 0.15 µg/ml) but not ceftriaxone (IC₅₀ 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.

Antimicrobial Agents and Chemotherapy, October 2010, p. 4510-4512, Vol. 54, No. 10
0066-4804/10/$12.00+0     doi:10.1128/AAC.00590-10