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Comparative Study
, 54 (5), 1670-7

Affinity of Ceftaroline and Other Beta-Lactams for Penicillin-Binding Proteins From Staphylococcus Aureus and Streptococcus Pneumoniae

Affiliations
Comparative Study

Affinity of Ceftaroline and Other Beta-Lactams for Penicillin-Binding Proteins From Staphylococcus Aureus and Streptococcus Pneumoniae

K Kosowska-Shick et al. Antimicrob Agents Chemother.

Abstract

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 <or=1 microg/ml against all S. aureus isolates and were <or=0.25 microg/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 >or=4-fold higher 50% inhibitory concentrations (IC(50)s) (0.1 to 4 microg/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 (IC(50), 0.1 to 1 microg/ml), a primary target for cephalosporin PBP binding activity, and high affinities for PBP2B (IC(50), 0.5 to 4 microg/ml) and PBP1A (IC(50), 0.125 to 0.25 microg/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 beta-lactams tested. Ceftaroline bound to PBP2a in methicillin-resistant S. aureus (IC(50), 0.01 to 1 microg/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.

Figures

FIG. 1.
FIG. 1.
Competition assays for penicillin G binding to PBPs in MSSA (ATCC 29213).
FIG. 2.
FIG. 2.
Competition assays for ceftaroline binding to PBP2a in MRSA strains.
FIG. 3.
FIG. 3.
Competition assays for ceftaroline binding to PBPs from Streptococcus pneumoniae strains.

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