Affinity of ceftaroline and other beta-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 <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.
Kosowska-Shick
K
K
Department of Pathology, Hershey Medical Center, Hershey, PA 17033, USA.
McGhee
P L
PL
Appelbaum
P C
PC
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000502:physiology; D002439:Cefotaxime / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000378:metabolism / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology*; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D002439:Cefotaxime; D002511:Cephalosporins; D010400:Penicillin G; D047090:beta-Lactams; D000097583:Ceftaroline