β-Lactamases of Increasing Clinical Importance

Abstract

Resistance to β-lactam-containing antimicrobial agents continues to increase, frequently due to the presence of β-lactamases in Gram-negative bacteria. Over the past twenty-five years broad-spectrum enzymes such as TEM- and SHV­ variants and the metallo- β-lactamases have become more prolific. As a result of the ability of plasmids to continue to acquire additional resistance determinants, many of the -lactamase-producing Gram-negative pathogens have become multi-drug resistant. In combination with decreased permeability, the organisms can become virtually untreatable with current therapies. The major groups of β-lactamases that pose the most serious therapeutic problems include the extended­ spectrum β-lactamases, the plasmid-mediated cephalosporinases, the inhibitor-resistant TEM- or SHV­ derived β-lactamases and the carbapenem-hydrolyzing β-lactamases. Those enzymes that can be transferred on mobile elements are the most serious of the newer β-lactamases, and include enzymes in each of the four groups outlined above.