Beta-lactamases: current situation and clinical importance

Production of beta-lactamases is the most important means of bacterial resistance to beta-lactam antibiotics. The traditional, plasmid-mediated beta-lactamases were initially confined to Enterobacteriaceae but have now spread to other genera and species including Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. Extended-spectrum plasmid-mediated beta-lactamases have been identified in Enterobacteriaceae, particularly Klebsiella spp. and Escherichia coli. They are capable of hydrolyzing second- and third-generation cephalosporins and older beta-lactams. Chromosomally mediated beta-lactamases may be produced constitutively or induced by the presence of a beta-lactam. Mutation within the bacterial genome may lead to constitutive enzyme hyperproduction. Strains that produce these enzymes are resistant to practically all beta-lactams, with the exception of carbapenems. The wide-spread occurrence of antibiotic resistance dictates that therapies be judiciously chosen with attention to the resistance patterns of the causative organisms.