ß-Lactams: Mechanisms of Action and Resistance

Beta-lactam antibiotics are typically used to treat a broad spectrum of Gram-negative bacteria. Beta-lactamases produced by Gram-negative organisms are usually secreted.This animation starts with the explanation of bacterial cell wall synthesis, the process targeted by ß-Lactams. Structurally, most bacteria consist of a cell membrane surrounded by a cell wall and, for some bacteria, an additional outer layer. Internal to the cell membrane is the cytoplasm which contains ribosomes, a nuclear region and in some cases granules and/or vesicles. Depending on the bacterial species, a number of different external structures may be found such as a capsule, flagella and pili.
Although the inhibitor-resistant β-lactamases are not ESBLs, they are often discussed with ESBLs because they are also derivatives of the classical TEM- or SHV-type enzymes. These enzymes were at first given the designation IRT for inhibitor-resistant TEM β-lactamase; however, all have subsequently been renamed with numerical TEM designations. There are at least 19 distinct inhibitor-resistant TEM β-lactamases. Inhibitor-resistant TEM β-lactamases have been found mainly in clinical isolates of E. coli, but also some strains of K. pneumoniae, Klebsiella oxytoca, P. mirabilis, and Citrobacter freundii. Although the inhibitor-resistant TEM variants are resistant to inhibition by clavulanic acid and sulbactam, thereby showing clinical resistance to the beta-lactam—lactamase inhibitor combinations of amoxicillin-clavulanate (co-amoxiclav), ticarcillin-clavulanate (co-ticarclav), and ampicillin/sulbactam, they normally remain susceptible to inhibition by tazobactam and subsequently the combination of piperacillin/tazobactam, although resistance has been described. To date, these beta-lactamases have primarily been detected in France and a few other locations within Europe.

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