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

The Journal of Antimicrobial Chemotherapy
Hélène MoisanFrançois Malouin

Abstract

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. 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. 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 isolate...Continue Reading

References

Jun 6, 2007·The Journal of Antimicrobial Chemotherapy·Shazad MushtaqDavid M Livermore

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Citations

Aug 18, 2012·Molecular BioSystems·Haihong HaoZonghui Yuan
Aug 29, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas M FileGary E Stein
Aug 29, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·David J FarrellRonald N Jones
Dec 9, 2010·The Journal of Antimicrobial Chemotherapy·Donald BiekDirk A Thye
Apr 22, 2011·The Journal of Antimicrobial Chemotherapy·Joseph B Laudano
Apr 22, 2011·The Journal of Antimicrobial Chemotherapy·Ian A CritchleyDirk A Thye
Apr 22, 2011·The Journal of Antimicrobial Chemotherapy·George L Drusano
Jun 7, 2011·American Journal of Therapeutics·Kathryn A CulosShellee A Grim
Mar 6, 2013·Antimicrobial Agents and Chemotherapy·Alasdair P MacGowanKaren E Bowker
May 2, 2012·Therapeutics and Clinical Risk Management·Julian J Goodman, Stanley I Martin
Dec 18, 2010·Future Microbiology·Zeina A Kanafani
Jul 16, 2014·Current Microbiology·Karen GreenUNKNOWN Canadian Bacterial Surveillance Network (CBSN)
Sep 26, 2013·Antimicrobial Agents and Chemotherapy·Xavier HenryBernard Joris
Apr 2, 2014·Postgraduate Medicine·Alpesh N AminBradley M Sherman
May 19, 2012·Expert Opinion on Pharmacotherapy·Anthony M CasapaoMichael J Rybak
Nov 5, 2015·Expert Opinion on Investigational Drugs·Cuong VuongMichael Otto
Nov 14, 2015·The Journal of Antimicrobial Chemotherapy·Ravina KullarSebastiaan J van Hal
Aug 2, 2015·Current Opinion in Pharmacology·Laura MorataAlex Soriano
Jan 28, 2016·Protein Science : a Publication of the Protein Society·Dustin T KingNatalie C J Strynadka
Oct 5, 2010·Current Opinion in Microbiology·Leticia I LlarrullShahriar Mobashery
Nov 25, 2014·Diabetes/metabolism Research and Reviews·B A LipskyE J C Goldstein
Sep 1, 2015·The Journal of Antimicrobial Chemotherapy·David M LivermoreNeil Woodford
Jun 4, 2015·Annual Review of Biochemistry·Sharon J Peacock, Gavin K Paterson

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