Antistaphylococcal activity of the novel cephalosporin CB-181963 (CAB-175).

MILLER, Keith, STOREY, Christopher, STUBBINGS, William J, HOYLE, Anthony M, HOBBS, Joanne K and CHOPRA, Ian (2005). Antistaphylococcal activity of the novel cephalosporin CB-181963 (CAB-175). The Journal of antimicrobial chemotherapy, 55 (4), 579-582.

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Link to published version:: https://doi.org/10.1093/jac/dki003
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    Abstract

    OBJECTIVES : We examined the antistaphylococcal activity of the novel cephalosporin CB-181963 (formerly known as CAB-175), with emphasis on its microbiological activity and penicillin-binding protein specificities.

    METHODS : Using established procedures, we examined the activity of CB-181963 against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of Staphylococcus aureus in both planktonic and biofilm culture. We also determined whether CB-181963 exhibited a post-antibiotic effect (PAE). A radioactive competition assay with (3)H-labelled benzylpenicillin was used to determine penicillin-binding protein (PBP) affinities of CB-181963, including binding to PBP2a from MRSA. The potential for emergence of CB-181963-resistant mutants in MSSA and MRSA strains was examined using plating procedures.

    RESULTS : CB-181963 showed excellent activity against MRSA strains resistant to other cephalosporins in both planktonic and biofilm cultures. However, in common with other cephalosporins it was unable to eradicate biofilms. CB-181963 had a short PAE compared with other beta-lactam antibiotics. CB-181963 retained activity against a strain expressing type A beta-lactamase and demonstrated affinity for PBP2a of MRSA. Mutants resistant to CB-181963 were not recovered in either MSSA or MRSA.

    CONCLUSIONS : CB-181963 is a potent antistaphylococcal agent with better activity against MRSA than other cephalosporins. The anti-MRSA activity is correlated with elevated binding to PBP2a. CB-181963 may have a role in the treatment of staphylococcal infections, including those caused by MRSA and in the prophylaxis of biofilm-associated MSSA and MRSA infections. However, because of its short PAE, CB-181963 may have to be administered more frequently than other beta-lactam antibiotics, or given via prolonged infusion.

    Item Type: Article
    Additional Information: First published online: February 18, 2005
    Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomolecular Sciences Research Centre
    Identification Number: https://doi.org/10.1093/jac/dki003
    Page Range: 579-582
    Depositing User: Jamie Young
    Date Deposited: 01 Jun 2015 11:14
    Last Modified: 13 Jun 2017 13:29
    URI: http://shura.shu.ac.uk/id/eprint/9965

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