0-Lactamase inhibitors classification

CD50, curative dose for 50% of mice following dosing subcutaneously all j8-lactamase inhibitors were inactive when dosed alone at the dose level used in the combination enzyme classification based upon Richmond-Sykes. For abbreviations, see footnote to Table 6.1. 

The most recent classification ofyff-lactamases is that of Bush [17], who proposed a modification of the Richmond-Sykes system based primarily on biochemical characteristics, using substrate and inhibitor profiles in addition to physical data. This system, which also includes yS-lactamases from Gram-positive bacteria, seems likely to become the preferred system for the classification of yS-lactamases in the future. 

Clavulanic acid is a mold product with only weak intrinsic antibacterial activity, but it is an excellent irreversible inhibitor of most (3-lactamases. It is believed to acylate the aotive site serine by mimioking the normal substrate. Hydrolysis occurs with some (3-lactamases, but in many cases, subsequent reactions ooour that inhibit the enzyme irreversibly. This leads to its classification as a mechanism-based inhibitor (or so-oalled suicide substrate). The precise chemistry is not well understood (Fig. 38.18), but when clavulanio acid is added to ampicillin and amoxicillin preparations, the potenoy against (3-lactamase-produoing strains is markedly enhanced. 

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