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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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:	Biomedical 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:	18 Mar 2021 18:45
URI:	https://shura.shu.ac.uk/id/eprint/9965

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