Affinity of ceftaroline and other beta-lactams for penicillin-binding proteins from Staphylococcus aureus and Streptococcus pneumoniae

Antimicrob Agents Chemother. 2010 May;54(5):1670-7. doi: 10.1128/AAC.00019-10. Epub 2010 Mar 1.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Binding, Competitive / physiology
  • Cefotaxime / metabolism
  • Cefotaxime / pharmacology
  • Ceftaroline
  • Cephalosporins / metabolism
  • Cephalosporins / pharmacology*
  • Drug Resistance, Microbial / physiology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Microbial Sensitivity Tests
  • Penicillin G / metabolism
  • Penicillin G / pharmacology*
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / metabolism
  • beta-Lactams / metabolism
  • beta-Lactams / pharmacology*


  • Anti-Bacterial Agents
  • Cephalosporins
  • beta-Lactams
  • Cefotaxime
  • Penicillin G