Beta Lactam Antibiotics

Beta Lactam Antibiotics

INTRODUCTION Beta-lactam antibiotics are among the most commonly prescribed drugs, grouped together based upon a shared structural feature, the beta-lactam ring. Beta-lactam antibiotics include:
* Penicillins
* Cephalosporins
* Cephamycins
* Carbapenems
* Monobactams
* Beta-lactamase inhibitors
Since this category of antibiotics is so broad, it is important to subdivide these drugs into functional drug groups to facilitate understanding and prescribing practices. It is not necessary for clinicians to know every drug within each of these groups. The grouping of these agents can be based upon spectrum of activity, for choice of agents for an antibiotic formulary, for therapeutic use or for routine susceptibility testing. Within each functional group, differences between antibiotics in pharmacokinetics, safety, duration of the clinical experience with their use, and cost allow reasonable choices to be made in selecting an individual drug as representative of that group.
The mechanisms of action and resistance and major adverse reactions to these antibiotics will be reviewed here. The penicillins, cephalosporins, and novel beta-lactam drugs are discussed separately. (See related topics).
MECHANISM OF ACTION Beta lactam antibiotics inhibit the growth of sensitive bacteria by inactivating enzymes located in the bacterial cell membrane, which are involved in the third stage of cell wall synthesis. It is during this stage that linear strands of peptidoglycan are cross-linked into a fishnet-like polymer that surrounds the bacterial cell and confers osmotic stability in the hypertonic milieu of the infected patient. Beta-lactams inhibit not just a single enzyme involved in cell wall synthesis, but a family of related enzymes (four to eight in different bacteria), each involved in different aspects of cell wall synthesis. These enzymes can be detected by their covalent binding of radioactively-labeled penicillin (or other beta-lactams) and hence have been called penicillin binding proteins (PBPs).
Different PBPs appear to serve different functions for the bacterial cell. As an example, PBP2 in Escherichia coli is important in maintaining the rod-like shape of the bacillus, while PBP3 is involved in septation during cell division [1]. Different beta-lactam antibiotics may preferentially bind to and inhibit certain PBPs more than others. Thus, different agents may produce characteristic effects on bacterial morphology and have different efficacies in inhibiting bacterial growth or killing the organism.