spp., particularly , are well-recognised bacterial pathogens. Production of the typical -lactamases of restricts the therapeutic use of -lactam agents mainly to the -lactamase inhibitor combinations and carbapenems. These compounds have the advantage of broad-spectrum activity and the ability to combat polymicrobial infections. Resistance of spp. to -lactam antibiotics appears to be increasing, largely because of an overall increase in -lactamase activity. There has been a rise in the prevalence of isolates showing high-level production of typical -lactamases and an increase in reports other potent -lactamase types. In the case of , metallo-enzymes are a particular threat to current therapeutic practice, as they are not inhibited by common -lactamase inhibitors and are able to hydrolyse carbapenems. The presence of permeability barriers may confer low-level -lactam resistance and supplement the effect of -lactamase activity. There are also sporadic reports of loss of -lactam activity because of reduced affinity of the penicillin-binding proteins.


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