Chapter 20: Antimicrobial Drugs

Antimicrobial Drugs

• Definition: Antimicrobial drugs inhibit microbial growth without causing significant damage to the host.

  • Selective Toxicity: The principle of differential toxicity to microbes versus their hosts.

  • Chemotherapy: Historical term for using these drugs.

  • Antibiotic: Refers to antimicrobial drugs derived from other microorganisms.

Sources of Antibiotics

• Gram-Positive Rods:

  • Bacillus subtilis: Produces Bacitracin

  • Paenibacillus polymyxa: Produces Polymyxin

  • Actinomycetes:

  • Streptomyces nodosus: Produces Streptomycin

  • Streptomyces venezuelae: Produces Erythromycin

  • Streptomyces aureofaciens: Produces Chlortetracycline and Tetracycline

  • Streptomyces griseus: Produces Gentamicin

  • Saccharopolyspora erythraea: Produces Amphotericin B

  • Micromonospora purpurea: Produces Gentamicin

• Fungi:

  • Cephalosporium spp.: Produces Cephalothin

  • Penicillium chrysogenum: Produces Penicillin

Antimicrobial Targets

• Broad-Spectrum Antibiotics: Effective against various microbes (may also affect normal microflora leading to superinfections).

• Narrow-Spectrum Antibiotics: Effective against limited types of microbes.

• Superinfection: Results from opportunistic pathogens due to the removal of normal flora by broad-spectrum antibiotics.

Mechanisms of Action of Antimicrobial Drugs

1. Inhibition of Cell Wall Synthesis:

   • Examples: Penicillins, Cephalosporins, Vancomycin.

2. Inhibition of Protein Synthesis:

   • Examples: Chloramphenicol, Erythromycin, Tetracyclines.

3. Injury to Plasma Membrane:

   • Example: Polymyxin B.

4. Inhibition of Nucleic Acid Replication and Transcription:

   • Examples: Quinolones, Rifampin.

5. Inhibition of Essential Metabolite Synthesis:

   • Examples: Sulfanilamide, Trimethoprim.

Specific Actions of Drugs by Mode

Cell Wall Synthesis Inhibitors

• Natural Penicillins: Penicillin G (injectable), Penicillin V (oral).

• Semisynthetic Penicillins: Oxacillin (resistant to penicillinase), Ampicillin (broad spectrum).

Protein Synthesis Inhibitors

• Chloramphenicol: Binds to the 50S ribosomal subunit, inhibiting peptide bond formation.

• Aminoglycosides (Streptomycin, Gentamicin): Bind to the 30S subunit, causing misreading of mRNA.

• Tetracyclines: Inhibit tRNA attachment.

Nucleic Acid Synthesis Inhibitors

• Rifampin: Blocks RNA polymerase in prokaryotes.

• Quinolones: Inhibit topoisomerase, thus preventing DNA replication.

Resistance to Antibiotics

• Mechanisms:

  1. Blocking Entry: Some bacteria modify their cell wall to prevent drug access.

  2. Enzymatic Destruction: Bacterial enzymes break down the antibiotic.

  3. Alteration of Target: Changes bacterial targets so antibiotics cannot bind effectively.

  4. Efflux Pumps: Bacteria pump out the antibiotics before they can exert their action.

Antifungal Drugs

• Function: Target fungal cells without harming human cells; exploit differences in cell membrane components.

  • Examples:

  • Polyenes: Amphotericin B.

  • Azoles: Miconazole.

  • Echinocandins: Inhibit beta-glucan synthesis in fungal cell walls.

Antiviral Drugs

• Nucleotide Analogues: Block viral DNA/RNA synthesis (e.g., Acyclovir).

• Enzyme Inhibitors:

  • Neuraminidase Inhibitors: Prevent release of new virions (e.g., for influenza).

• Entry/Fusion Inhibitors: Block virus from entering host cells.

Antibiotic Usage and Resistance

• Combination Therapy: Can have synergistic or antagonistic effects.

• Overuse and Misuse: Contribute significantly to the rise of resistant bacterial strains.

• New Developments: Ongoing synthesis and discovery of new antimicrobial substances from various organisms.