Abstract
β-lactams have a long history in the treatment of infectious diseases, though their use has been and continues to be confounded by the development of resistance in target organisms. β-lactamases, particularly in Gram-negative pathogens, are a major determinant of this resistance, although alterations in the β-lactam targets, the penicillin-binding proteins (PBPs), are also important, especially in Gram-positive pathogens. Mechanisms for the efflux and/or exclusion of these agents also contribute, though often in conjunction these other two. Approaches for overcoming these resistance mechanisms include the development of novel β-lactamase-stable β-lactams, β-lactamase inhibitors to be employed with existing β-lactams, β-lactam compounds that bind strongly to low-affinity PBPs and agents that potentiate the activity of existing β-lactams against low-affinity PBP-producing organisms.
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Received 9 February 2004; received after revision 30 March 2004; accepted 19 April 2004
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Poole, K. Resistance to β-lactam antibiotics. CMLS, Cell. Mol. Life Sci. 61, 2200–2223 (2004). https://doi.org/10.1007/s00018-004-4060-9
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DOI: https://doi.org/10.1007/s00018-004-4060-9