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Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Beta-lactams against methicillin-resistant Staphylococcus aureus.
Current Opinion in Pharmacology
Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to virtually all non-experimental antibiotics. They are intrinsically resistant to beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein 2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta-lactams, designing beta-lactams capable of blocking this additional target should help solve the issue. Older molecules including penicillin G, amoxicillin and ampicillin had relatively good PBP2A affinities, and successfully treated experimental endocarditis caused by MRSA, provided that the bacterial penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold greater PBP2A affinities and low minimal inhibitory concentrations were developed, primarily in the cephem and carbapenem classes. They are also very resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal models of infection, and two--the carbapenem CS-023 and the cephalosporin ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.
Animals, Clinical Trials as Topic, Humans, Methicillin Resistance/drug effects, Penicillin-Binding Proteins/antagonists & inhibitors, Penicillin-Binding Proteins/metabolism, Staphylococcus aureus/drug effects, Staphylococcus aureus/metabolism, beta-Lactams/pharmacokinetics, beta-Lactams/pharmacology
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