Activity of beta-lactamases against beta-lactams.

Resistance mediated by beta-lactamases is an important mechanism which has evolved in both Gram-positive and Gram-negative bacteria. There are a large number of different beta-lactamases produced by micro-organisms. Synthesis can be mediated by chromosomes, plasmids, or transposons. Enzyme kinetics for these different beta-lactamases are expressed as affinity of the enzyme for the substrate (1/Km) and rate of hydrolysis of the substrate by the enzyme (Vmax). Such kinetics at physiological concentrations of the enzyme and substrate are important factors in determining the activity of beta-lactam agents. Other factors include the cellular location and amount of enzyme. The clinical importance of subtle differences in beta-lactamase-mediated resistance for both Gram-positive and Gram-negative bacteria is becoming apparent. Antagonism of beta-lactams by beta-lactamases becomes increasingly more important as a resistance mechanism as our knowledge and understanding of this phenomenon grows.