BETA-LACTAMASE INHIBITORS - AGENTS TO OVERCOME BACTERIAL-RESISTANCE

The extensive use of beta-lactam antibiotics in hospitals and communit y has created major resistance problems leading to increased morbidity , mortality and health-care costs. Resistance is most often mediated b y -lactamases, which have emerged in both Gram-positive and Gram-negat ive bacteria. A novel approach to countering bacterial beta-lactamases is the delivery of a beta-lactam antibiotic in combination with a bet a-lactamase inhibitor. Several such combinations are currently availab le, containing inhibitors clavulanic acid, sulbactam and tazobactam. T hese inhibitors are not, however, active against all beta-lactamases a nd the AmpC chromosomal enzymes that are hyperproduced by some enterob acteria and pseudomonas are a particular 'gap'. Moreover, genes for th ese AmpC enzymes have begun to escape to plasmids. consequently, there is a growing need for new broad-spectrum beta-lactamase inhibitors. T his review offers an overview of synthetic beta-lactamase inhibitors, emphasizing information on their structures, and highlighting their ac tivity against various beta-lactamases, particularly AmpC enzymes. Eff ective inhibition of AmpC enzymes are to be found among the penems and monobactams, but none of these has yet proved suitable for pharmaceut ical development.