Beta-lactam Information & Beta-lactam Links at HealthHaven.com

[edit] Clinical significance

The beta-lactam ring is part of the structure of several antibiotic families, principally the penicillins, cephalosporins, carbapenems and monobactams, which are therefore also called beta-lactam antibiotics. These antibiotics work by inhibiting the bacterial cell wall synthesis. This has a lethal effect on bacteria, especially on Gram-positive ones. Bacteria can become resistant against beta-lactam antibiotics by expressing beta-lactamase.

[edit] History

The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline and benzaldehyde with diphenylketene^[2] ^[3] in a [2+2]cycloaddition:

[edit] Beta-lactam resistance

Because of the popularity of beta-lactam drugs, certain bacteria have been able to develop counter-measures to traditional drug therapies. An enzyme called beta-lactamase is present in many different types of bacteria, which serves to 'break' the beta lactam ring, which effectively nullifies the antibiotic's effectiveness.

As a response to bacterial resistance to beta-lactam drugs, there are drugs, such as Augmentin/CLAMP, which are designed to disable the beta-lactamase enzyme. Augmentin/CLAMP (FGP) is made of amoxicillin, a beta-lactam antibiotic, and clavulanic acid, a beta-lactamase inhibitor. The clavulanic acid is designed to overwhelm all beta-lactamase enzymes, bind irreversibly to them, and effectively serve as an antagonist so that the amoxicillin is not affected by the beta-lactamase enzymes.

[edit] Secondary beta-lactam drug resistance

As a response to decreased efficacy of beta-lactamase, some bacteria have changed the proteins that beta-lactam antibiotics bind, the penicillin binding proteins (PBPs). Since the PBPs no longer recognize the beta-lactams, the antibiotics are essentially useless. This is the mechanism behind the methicillin-resistant Staphylococcus aureus (MRSA).

[edit] Mechanism

Penicillin, a beta-lactam, binds to and inactivates a bacterium's penicillin binding protein (PBP), also known as transpeptidases. PBPs vary in their affinity for binding penicillin or other beta-lactam antibiotics. The amount of PBPs varies between bacterial species. PBPs form transpeptidase bonds in the absence of penicillins or other beta-lactam antimicrobics.

[edit] Side effects

The most common side effect of beta-lactams is fever. Eosinophilia and rash accompany the fever in 25% of patients.

[edit] See also

[edit] External links

Synthesis of beta-lactams

[edit] References

^ Gilchrist, T. (1987). Heterocyclic Chemistry. Harlow: Longman Scientific. ISBN 0582014212.
^ Tidwell, Thomas T. (2008). "Hugo (Ugo) Schiff, Schiff Bases, and a Century of β-Lactam Synthesis". Angewandte Chemie International Edition 47: 1016. doi:10.1002/anie.200702965.
^ H. Staudinger, Justus Liebigs Ann. Chem. 1907, 356, 51 – 123.

[0] Gilchrist, T. (1987). Heterocyclic Chemistry. Harlow: Longman Scientific. ISBN 0582014212.

[1] Tidwell, Thomas T. (2008). "Hugo (Ugo) Schiff, Schiff Bases, and a Century of β-Lactam Synthesis". Angewandte Chemie International Edition 47: 1016. doi:10.1002/anie.200702965.

[2] H. Staudinger, Justus Liebigs Ann. Chem. 1907, 356, 51 – 123.

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