title: Binding of ceftaroline to penicillin-binding proteins of Staphylococcus aureus and Streptococcus pneumoniae.
abstract: OBJECTIVE
  This study evaluated the affinity of ceftaroline and comparator beta-lactams for penicillin-binding proteins (PBPs) of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and Streptococcus pneumoniae with varying susceptibility to penicillin. Ceftaroline is currently in Phase 3 development for the treatment of complicated skin and skin structure infections and community-acquired pneumonia, including infections caused by MRSA and multidrug-resistant S. pneumoniae.
  
  
  METHODS
  Binding affinities (IC(50)s) of ceftaroline, ceftriaxone, oxacillin and penicillin G for PBPs were measured in a competition assay by adding various concentrations of the test drugs to membranes or whole cells. PBPs were labelled using the fluorescent reporter molecule Bocillin FL.
  
  
  RESULTS
  Overall, ceftaroline exhibited greater binding affinity for the range of PBPs tested, as compared with comparator beta-lactams. The high affinity of ceftaroline for PBPs 1-3 of MSSA and PBP2a of MRSA correlates well with its efficacy against these organisms, as determined by MIC. Similarly, efficient binding of ceftaroline to key S. pneumoniae PBPs, such as PBP2x/2a/2b, taken together, correlates well with its low MICs for penicillin-resistant isolates of S. pneumoniae.
  
  
  CONCLUSIONS
  The high affinities of ceftaroline for MRSA PBP2a, MSSA PBPs 1-3 and S. pneumoniae PBP2x/2a/2b support the potential efficacy of ceftaroline in the treatment of infections caused by MRSA and S. pneumoniae.
authors.affiliation: Centre d'Etude et de Valorisation de la Diversité Microbienne, Département de Biologie, Université de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1.
authors.forename: Hélène
authors.initials: H
authors.lastname: Moisan
authors.forename: Mireille
authors.initials: M
authors.lastname: Pruneau
authors.forename: François
authors.initials: F
authors.lastname: Malouin
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D046915:Penicillin-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000097583:Ceftaroline