Journal Article

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

Keith Miller, Christopher Storey, William J. Stubbings, Anthony M. Hoyle, Joanne K. Hobbs and Ian Chopra

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 4, pages 579-582
Published in print April 2005 | ISSN: 0305-7453
Published online April 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki003
Antistaphylococcal activity of the novel cephalosporin CB-181963 (CAB-175)

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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 3H-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 β-lactam antibiotics. CB-181963 retained activity against a strain expressing type A β-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 β-lactam antibiotics, or given via prolonged infusion.

Keywords: methicillin-resistant Staphylococcus aureus; penicillin-binding proteins

Journal Article.  1907 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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