Cell Wall Synthesis Inhibitors: 3

Imipenem – Broad spectrum of activity that includes Pseudomonas, Actineobacter, and anaerobes (B. fragilis); given with cilastin to prevent inactivation by renal dipeptidase.

Beta-Lactamase Inhibitors

Clavulanic acid, Sulbactam & Tazobactam – Suicide inhibitors of Beta-lactamases.

Clavulanic acid is used amoxicillin and is the treatment of choice for bite wound infections.

Piperacillin/tazobactam sodium, Ticaricillin/clavulanate potassium.

Aztreonam – Resistant to Beta-lactamase; useful only for G(-); can lead to superinfection.

Miscellaneous

Cycloserine – MOA is inhibition of racemase; used in combination treatment of tuberculosis.

Vancomycin –

• MOA inhibits cell wall synthesis by binding the D-alanyl-D-alanine dipeptide in cell walls and thus inhibits peptidoglycan synthesis by interfering with transfer of the peptide.
• Bactericidal.
  
• Limited to treatment of S. aureus infections that are resistant to less toxic agents as well as C. difficile infections.
  
• Toxicities are like the aminoglycosides and include ototoxicity, peripheral neuropathies, and injection irritation.

Polypeptides

General: All are nephrotoxic and parenteral administration is reserved for special, difficult clinical situations.

Bacitracin – MOA is inhibition of cell wall synthesis by inhibiting pyrophosphatase reaction. Use is limited to topical application for treatment of staph infections. Intrathecal or intrapleural instillation reserved for treatment of resistant-penicillin Staphylococcal meningitis or empyema. Toxicities include nephrotoxicity and eosinophilia.

Polymixin B sulfate – MOA is disruption of cell plasma membrane. Main used is topical against G(-) bacilli. Effective against a host of organisms but toxicity is severe (curare-like effect, nephrotoxicity, phlebitis).

Colistin sulfate – Same as polymixin.

Drug interactions

Carbenicillin-Gentamicin – Antagonistic effect.

Penicillin-Chlortetracycline – Theory says no, practice says okay.

Ampicillin-Oral contraceptive – Breakthrough bleeding and loss of contraceptive power.

Cefoperazone/Moxolactam/Cefamandole-Alcohol – Disulfiram-like reaction.

Category: Pharmacology Notes