Affinity of Ceftaroline and Other β-Lactams for Penicillin-Binding Proteins from Staphylococcus aureus and Streptococcus pneumoniae

We compared the affinities of ceftaroline for all penicillin-binding proteins (PBPs) with those of ceftriaxone and cefotaxime in 6 Staphylococcus aureus and 7 Streptococcus pneumoniae isolates with various resistance phenotypes. Ceftaroline MICs were ≤1 μg/ml against all S. aureus isolates and were ≤0.25 μg/ml for 4 of 7 isolates of S. pneumoniae. Ceftaroline affinities for penicillin-susceptible S. pneumoniae strains were in the order PBP2X and -3 > PBP1A, -1B, and -2A > PBP2B, and ceftaroline had ≥4-fold higher 50% inhibitory concentrations (IC50s) (0.1 to 4 μg/ml) for PBP2X, -2A, -2B, and -3 than those for the other cephalosporins tested. Among 3 penicillin-resistant S. pneumoniae strains, ceftaroline had a high affinity for PBP2X (IC50, 0.1 to 1 μg/ml), a primary target for cephalosporin PBP binding activity, and high affinities for PBP2B (IC50, 0.5 to 4 μg/ml) and PBP1A (IC50, 0.125 to 0.25 μg/ml) as well, both of which are also known as major targets for PBP binding activity of cephalosporins. Ceftaroline PBP affinities in methicillin-susceptible S. aureus strains were greater than or equal to those of the 3 other β-lactams tested. Ceftaroline bound to PBP2a in methicillin-resistant S. aureus (IC50, 0.01 to 1 μg/ml) with up to 256-fold-higher affinity than those of other agents. Ceftaroline demonstrated very good PBP affinity against all S. aureus and S. pneumoniae strains tested, including resistant isolates.