Antimicrobial Agents Overview

Antimicrobial Agents

• Antimicrobial agents are substances that kill or inhibit the growth of microorganisms.
• Antibiotics are a type of antimicrobial substance produced by living microorganisms.
• In 1877, Pasteur and Joubert observed that airborne contaminants had a lethal effect on Bacillus anthracis.
• In 1929, Alexander Fleming observed that the fungus Penicillium notatum inhibited the growth of staphylococci.
• Chain, Florey, and associates developed penicillin preparations with high antibacterial therapy but low toxicity for humans and animals.
• A major source of antibiotics is Streptomyces.
• Antibiotics are classified by their effect on bacteria.
  • Bactericidal antibiotics kill bacteria.
    • Examples include penicillin, streptomycin, cephalosporin, polymyxin, neomycin, and erythromycin.
    • These have a rapid lethal effect in high concentrations.
  • Bacteriostatic antibiotics inhibit bacterial growth.
    • Examples include tetracyclines, sulfonamides, and chloramphenicol.
    • Some can be both.

Mechanism of Action

• Sulfonamides are bacteriostatic, inhibiting the growth of bacteria by acting as structural analogs of PABA.

  • PABA is essential for the synthesis of folic acid, an essential metabolite for bacteria.
  • Sulfonamides compete with PABA, hindering folic acid synthesis and consequently, inhibiting bacterial growth.
    • However, they do not affect bacteria that cannot synthesize their own folic acid.

• Penicillins inhibit the synthesis of cell walls in growing susceptible bacteria.

  • Bacteria's cell wall is composed of peptidoglycan.
  • Penicillins prevent crosslinking of peptidoglycan, resulting in cell lysis.
    • Bacteria that lack cell walls are not affected.
    • Different procaine chains can influence the absorption.

• Cephalosporins are synthetic analogs of penicillin.

  • They have a lower toxicity and broader spectrum of activity than penicillins.
  • They are effective against gram-positive and gram-negative bacteria.

• Aminoglycosides inhibit protein synthesis.

  • These bind to the 30S ribosomal subunit and interfere with the protein synthesis process within the cell.
    • This results in miscodding of proteins and peptide elongation.
  • Potential mechanisms cause impaired ribosomal binding, transport, alteration/inactivation of the drug.

• Tetracyclines inhibit protein synthesis.

  • Bind to 30S ribosomal subunits and prevent the function of tRNA, which is crucial for protein production.
    • It is bacteriostatic and has a broad spectrum of effectiveness.

• Chloramphenicol inhibits protein synthesis.

  • Binds to 50S ribosomal subunits to suppress protein production.
    • Prolonged use may lead to bone marrow depression.

• Macrolides (e.g., erythromycin) also inhibit protein synthesis. -Bind to 50S ribosome.

• Lincosamides (e.g., clindamycin) also inhibit protein synthesis.

  • Bind to a 50S ribosomal subunit.

• Quinolones inhibit certain activities involving DNA.

  • Inhibit the bacterial enzyme DNA gyrase, an activity crucial for supercoiling of chromosomal DNA.
    • This results in the degradation of DNA; resulting in bacterial death.

Mechanisms of Drug Resistance

• Mechanisms for drug resistance include changes in outer membrane permeability, alterations in DNA gyrase, altered metabolic pathways, generation of antibiotic destroying enzymes, and alteration in the target.