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The history of medical attempts to combat the effects of bacterial infection over the last century has been characterised by the discovery of agents with antimicrobial activity, and their widespread introduction into clinical practice to treat infection, with dramatic effects on morbidity and mortality. This has been followed by the development of resistance mutations in the pathogens, rendering these agents impotent and necessitating the development of new agents which circumvent these mechanisms of resistance.
The production of β-lactamase by bacteria has long been recognised as an important mechanism by which they can neutralise the action of penicillins. These enzymes are encoded on plasmids, rather than in chromosomal nucleic acid, thus enabling rapid transmission of resistance between bacterial species.1 β-Lactamase production is now common in Staphylococcus, Haemophilus influenzae, Neisseria gonorrhoeae and a wide variety of Gram-negative coliforms. Antibiotics have now been developed which are able to resist these β-lactamases oxyimino β lactams such as cephalosporins, and monobactams which were introduced into clinical practice in 1981. These have an oxyimino side chain which prevents β-lactamase from binding. An alternative strategy was the development of β-lactamase inhibitors such as clavulinic acid and sulbactam, and combining them with agents which had become ineffective when acting alone (eg, co-amoxyclav)2
What are ESBLs?
ESBLs are viewed as new β-lactamases, although they were first described in Germany as long ago as 1983.3 They are able to hydrolyse the oxyimino group, thus conferring resistance to most β-lactam antibiotics, except for carbapenems (eg, meropenem) and cephamycins (a class not in common use in the UK). They are inhibited by β-lactamase inhibitors, and this property assists their identification in the microbiology laboratory, distinguishing them from other resistance mechanisms—for example, AmpC. They are often encoded on large plasmids, which means that additional resistance mutations can be carried by the …
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