INHIBITION OF CELL WALL SYNTHESIS

Bacterial Cell Wall Synthesis

• New peptidoglycan monomers are inserted by transglycosylase (transglycosidase)

• The final rigidity of the cell wall is imparted by cross-linking of the peptide chains by transpeptidase enzyme

Penicillin-Binding Proteins (PBP)

may act as transglycosylase or as transpeptidase

β-Lactam Drugs

• All ___ drugs are selective inhibitors of bacterial cell wall synthesis

• Destruction of bacterial autolysins (murein hydrolase)

• Core structure of penicillins (top) and cephalosporins (bottom) ___ ring in red.

memo the gen

Penicillins

The ___ are derived from molds of the genus Penicillium

1.  Natural Penicillins 

2. β-lactamase resistant 

3. Aminopenicillins 

4. Ureidopenicillins 

5. Carboxypenicillins

5 Principal Groups of penicillin

Natural Penicillins

They have the highest activity against Gram-positive organisms, spirochetes, and susceptible to β lactamase

• Penicillin V (phenoxymethylpenicillin)

• Penicillin G (Benzylpenicillin)

•  Aqueous penicillin G (IV) 

• Procaine penicillin G (IM) 

• Benzathine penicillin G (IM)

Penicillin G (Benzylpenicillin)

β-Lactamase Resistant

• Antistaphylococcal penicillins

• Lower activity against Gram-positive organisms and inactive against Gram-negative organisms.

   o Nafcillin, Methicillin, Oxacillin, Dicloxacillin

• Staphylococci resistant to oxacillin and nafcillin have the mecA gene

Aminopenicillins

• Extended-Spectrum Penicillins

• They have high activity against both Gram-positive and Gram-negative organisms but are destroyed by βlactamases

• Ampicillin

• Amoxicillin

Aminopenicillins + β-Lactamase Inhibitors

• Ampicillin + Sulbactam (Sultamicillin)

• Amoxicillin + Clavulanic acid (Co-Amoxiclav)

Ureidopenicillins

• Piperacillin (anti-pseudomonal)

• Mezlocillin

Carboxypenicillins – anti-pseudomonal

• Carbenicillin

• Ticarcillin

• Piperacillin + Tazobactam

• Ticarcillin + Clavulanic acid

Other preparations:

Cephalosporins

• The mechanism of action is analogous to that of penicillins

• ___ tend to be resistant to the βlactamases

• ___ have been arranged into major groups, or “generations”

1st Generation

Gram (+) cocci and PEcK (P. mirabilis, E. coli, K. pneumoniae)

2nd Generation

Gram (+) cocci and HENPEcK (H. influenzae, E. aerogenes, N. gonorrhae, P. mirabilis, E. coli, K. pneumoniae)

3rd Generation

Gram (+) cocci and HENPPEcK (H. influenzae, E. aerogenes, N. gonorrhae, P. aeruginosa, P. mirabilis, E. coli, K. pneumoniae

4th Generation

Gram (+) cocci [MRSA] and E. coli, K. pneumoniae, P. mirabilis, and P. aeruginos

Carbanepams

• Imipenem + Cilastatin – has good activity against many Gram-negative rods, Gram-positive organisms, and anaerobes.

• Meropenem

• Ertapenem

Monobactams

• Aztreonam

• It has antimicrobial activity directed primarily against the Enterobacteriaceae, including P. aeruginosa.

• No activity against Gram-positive organisms and anaerobes

Other Cell Wall Synthesis Inhibitors

• Glycopeptide antibiotics such as vancomycin and teicoplanin

• Lipoglycopeptides such as oritavancin, telavancin, and dalbavancin.

• Fosfomycin

• Bacitracin

• Cycloserine

• Novobiocin

penicillin

cephalosporins

carbapenems

Monobactam

Vancomycin

Penicillin cephalosporins

Type of act: bactericidal

Vancomycin bacitracin

process: mucopeptide synthesis
type of act: bactericidal

cycloserine

process: synthesis of cell wall peptides
type of act: bactericidal