Beta-lactams Antibiotics

Beta-lactam antibiotics are antimicrobials whose functional portions are called beta-lactam (B-lactam) rings. Beta-lactams inhibit peptidoglycan formation by irreversibly binding to the enzymes that cross-link NAM subunits. They include: penicillins, cephalosporins, carbapenems and monobactams (Aronson, 2006).
1. Penicillins:
Penicillin exerts its effect by forming a covalent bond with penicillin-binding proteins (PBPs), which are critical for assembly of the cell wall (Chambers, 2000).
The PBPs are trans-peptidases which catalyze the cross linking reaction between two stem peptides, each linked to adjacent N-acetylmuramic acid residues of the peptidoglycan backbone. This reaction which cross links the penultimate D-alanine residue of one peptide (the donor) with the third L-lysine residue of the next peptide (the acceptor) with elimination of the ultimate D-alanine of the donor, is responsible for conferring rigidity to the cell wall. Penicillins which are structurally similar to the D-alanyl-D-alanine (D-Ala–D-Ala) dipeptide form fairly stable covalent complexes with PBPs and thereby inhibit the cross linking reaction, resulting in the weakening of the cell wall and ultimate lyses of the cell (Zapun et al., 2008).
All penicillins share the same basic structure (6-aminopenicillanic acid). A thiazolidine is attached to a β-lactam ring that carries a free amino group. Modification of the side chain of penicillins permits improved penetration through the porins in the cell envelope, resulting in enhanced antibacterial spectrum (Reddy, 2009a).
The clinically important penicillins fall into four principal groups (Brooks and Carrol, 2010):
1. Highest activity against gram-positive organisms and spirochetes but susceptible to hydrolysis by β-lactamases and acid labile (e.g., penicillin G).
2. Relative resistance to β-lactamases but lower activity against gram-positive organisms and inactivity against gram-negative organisms (e.g., nafcillin).
3. Relatively high activity against both gram-positive and gram-negative organisms but destroyed by β-lactamases (e.g., ampicillin, piperacillin).
4. Relative stability to gastric acid and suitable for oral administration (e.g., penicillin V, cloxacillin, amoxicillin).
2. Cephalosporins:
They are chemically similar to penicillins (with a nucleus of 7-aminocephalospranic acid instead of 6-aminopenicillanic acid) and acts in the same way as penicillins. They are more stable to many bacterial β-lactamases and this property has been increased with the latter generations of the drug. Cephalosporins are effective against gram-positive and gram-negative bacteria and variations in the side chains of β-lactam ring can alter the antibacterial activity (Asbel and Levison, 2000).


3. Carbapenems:
Carbapenems (imipenem, meropenem, and faropenem) diffuse more readily through the outer membrane of most gram-negative bacteria and they are also generally less readily inactivated by β-lactamases than other β-lactams (Zhanel et al., 2007).
4. Monobactams:
Monobactams (aztereonam) have a mono cyclic β-lactam ring and are resistant to β-lactamases, but they are active only against aerobic gram-negative bacteria because they do not bind to PBPs in gram-positive bacteria or anaerobes (Asbel and Levison, 2000).
Manual of Antibiotics: Method of Actions, Mechanisms of Resistance and Relations to Health Care associated Infections