Format

Send to

Choose Destination
J Antimicrob Chemother. 2010 Apr;65(4):713-6. doi: 10.1093/jac/dkp503. Epub 2010 Jan 22.

Binding of ceftaroline to penicillin-binding proteins of Staphylococcus aureus and Streptococcus pneumoniae.

Author information

1
Centre d'Etude et de Valorisation de la Diversité Microbienne, Département de Biologie, Université de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1.

Abstract

OBJECTIVES:

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.

PMID:
20097788
DOI:
10.1093/jac/dkp503
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center