Understanding the longevity of the β-lactam antibiotics and of antibiotic/β-lactamase inhibitor combinations

Microbial resistance necessitates the search for new targets and new antibiotics. However, it is likely that resistance problems will eventually threaten these new products and it may, therefore, be instructive to review the successful employment of β-lactam antibiotic/β-lactamase inhibitor combinat...

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Bibliographic Details
Published in:Biochemical pharmacology 2006-03, Vol.71 (7), p.930-940
Main Author: Buynak, John D.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibiotic
beta-Lactam Resistance - drug effects
beta-Lactam Resistance - physiology
beta-Lactamase Inhibitors
Drug Combinations
Drug Design
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Inhibitor
Lactams - chemistry
Lactams - pharmacology
Mechanism
Resistance
β-Lactam
β-Lactamase
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Summary:Microbial resistance necessitates the search for new targets and new antibiotics. However, it is likely that resistance problems will eventually threaten these new products and it may, therefore, be instructive to review the successful employment of β-lactam antibiotic/β-lactamase inhibitor combinations to combat penicillin resistance. These combination drugs have proven successful for more than two decades, with inhibitor resistance still being relatively rare. The β-lactamase inhibitors are mechanism-based irreversible inactivators. The ability of the inhibitors to avoid resistance may be due to the structural similarities between the substrate and inhibitor.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2005.11.012