Cephalosporins

Mechanism of action

The mechanism of action of cephalosporins involves inhibiting bacterial cell wall synthesis, leading to the death or inhibition of bacterial growth.

Here is a step-by-step breakdown of how cephalosporins work:

1. Binding to Penicillin-Binding Proteins (PBPs): Cephalosporins have a similar structure to penicillins, and they target the penicillin-binding proteins (PBPs) present in the bacterial cell wall. PBPs are enzymes that play a crucial role in synthesizing and remodeling the bacterial cell wall.

2. Inhibition of Transpeptidation: Cephalosporins bind to the PBPs, particularly the transpeptidase enzymes. These enzymes are responsible for cross-linking the peptidoglycan strands, a crucial step in the formation and stability of the bacterial cell wall. By binding to the transpeptidase enzymes, cephalosporins prevent the cross-linking process.

3. Impaired Cell Wall Formation: As a result of the transpeptidation inhibition, the formation of the bacterial cell wall is disrupted. The cell wall loses its structural integrity and becomes weak.

4. Activation of Autolytic Enzymes: Cephalosporins also stimulate the activation of autolytic enzymes, such as autolysins, which are naturally occurring enzymes in bacteria. These enzymes break down the existing peptidoglycan in the bacterial cell wall.

5. Cell Lysis and Death: The combination of impaired cell wall synthesis and activation of autolytic enzymes leads to the weakening and eventual lysis (rupture) of the bacterial cell wall. Without a functional cell wall, the bacteria are unable to maintain their shape and integrity, ultimately resulting in cell death.

Classification

Cephalosporins are classified into five generations based on their development and spectrum of activity. 

1. First-generation cephalosporins: These cephalosporins have a narrower spectrum of activity and are primarily effective against Gram-positive bacteria, including some strains of Staphylococcus and Streptococcus. Examples include cefazolin and cephalexin.

2. Second-generation cephalosporins: Second-generation cephalosporins have an expanded spectrum of activity compared to first-generation cephalosporins. They retain activity against Gram-positive bacteria and have improved activity against some Gram-negative bacteria. Examples include cefuroxime and cefaclor.

3. Third-generation cephalosporins: Third-generation cephalosporins have an even broader spectrum of activity, particularly against Gram-negative bacteria, including Enterobacteriaceae (such as Escherichia coli and Klebsiella) and Haemophilus influenzae. They also maintain activity against some Gram-positive bacteria. Examples include ceftriaxone and ceftazidime.

4. Fourth-generation cephalosporins: Fourth-generation cephalosporins have a similar spectrum of activity against Gram-negative bacteria as third-generation cephalosporins, but they have increased stability against bacterial enzymes that can break down the antibiotic. They also retain activity against some Gram-positive bacteria. Examples include cefepime.

5. Fifth-generation cephalosporins: Fifth-generation cephalosporins are the most recent addition to the cephalosporin class. They have an expanded spectrum of activity against both Gram-positive and Gram-negative bacteria, including resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and certain Enterobacteriaceae. Examples include ceftaroline and ceftobiprole.