Abstract | OBJECTIVES: 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: 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.
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Authors | Keith Miller, Christopher Storey, William J Stubbings, Anthony M Hoyle, Joanne K Hobbs, Ian Chopra |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 55
Issue 4
Pg. 579-82
(Apr 2005)
ISSN: 0305-7453 [Print] England |
PMID | 15722396
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Bacterial Proteins
- CB 181963
- Carrier Proteins
- Cephalosporins
- Penicillin-Binding Proteins
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Topics |
- Anti-Bacterial Agents
(metabolism, pharmacology)
- Bacterial Proteins
(physiology)
- Biofilms
(drug effects)
- Carrier Proteins
(physiology)
- Cephalosporins
(metabolism, pharmacology)
- Methicillin Resistance
- Microbial Sensitivity Tests
- Penicillin-Binding Proteins
(metabolism)
- Protein Binding
(physiology)
- Staphylococcus aureus
(drug effects, metabolism)
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