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. 1992 May;14(5):1089-99.
doi: 10.1093/clinids/14.5.1089.

beta-Lactamases of Gram-Negative Bacteria: New Challenges for New Drugs


beta-Lactamases of Gram-Negative Bacteria: New Challenges for New Drugs

C C Sanders. Clin Infect Dis. .


The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor. The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria. These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases. In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids. There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance. Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance.

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