beta-lactamases of increasing clinical importance

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