10.06 Antibiotics

Antibiotics

Definition:

• Antibiotic: A drug derived from a living organism that kills or inhibits the growth of bacteria without harming the cells of the infected organism.

Types of Antibiotics

1. Naturally Derived:
   • Originated from organisms (e.g., fungi, bacteria).
   • Often chemically modified to enhance effectiveness.
   • Example: Penicillin.
2. Synthetic Antibiotics:
   • Fully lab-made.
   • Designed to target specific bacterial processes.
   • Example: Isoniazid (used in tuberculosis treatment).

Mechanism of Action

• Antibiotics target bacterial cell growth or metabolism by disrupting one or more of the following:

1. Cell Wall Synthesis:
   • Penicillin: Inhibits peptidoglycan cross-linking, weakening the cell wall and causing bacterial cells to burst.
2. Cell Membrane Integrity:
   • Polymyxin: Damages the bacterial cell membrane, leading to cell death.
3. Enzyme Activity:
   • Sulfa Drugs: Inhibit bacterial enzymes involved in metabolic pathways.
4. Protein Synthesis:
   • Tetracycline, Streptomycin, Erythromycin: Interfere with bacterial ribosomes, preventing protein synthesis.
5. DNA/RNA Synthesis:
   • Quinolones: Disrupt DNA replication by targeting bacterial DNA gyrase.

Example of Cell Wall Targeting:

• Penicillin:
  • Inhibits enzymes responsible for cross-linking peptidoglycan in bacterial cell walls.
  • Effective only on growing bacteria, as it prevents the closure of small holes formed during cell wall expansion, leading to cell lysis.

Why Antibiotics Don’t Work on Human Cells or Viruses

• Human Cells:
  • Lack cell walls.
  • Utilize different proteins and metabolic pathways not targeted by antibiotics.
• Viruses:
  • Lack cellular structures like cell walls and ribosomes.
  • Rely entirely on host cell machinery for replication, which antibiotics do not affect.

Antibiotic Resistance

Definition:

• The ability of bacteria to survive and proliferate in the presence of an antibiotic that would normally inhibit or kill them.

Mechanisms of Resistance:

1. Thick Cell Walls:
   • Example: Mycobacterium tuberculosis has a thick, impermeable cell wall that blocks antibiotic entry.
2. Enzyme Production:
   • Example: β-lactamase enzymes break down penicillin, rendering it ineffective.
3. Efflux Pumps:
   • Bacterial membrane proteins that actively pump antibiotics out of the cell.
4. Mutation in Binding Sites:
   • Changes in the antibiotic’s target site prevent effective binding and action.

Spread of Resistance Genes:

• Plasmids:
  • Small, circular DNA molecules carrying resistance genes.
  • Transferred between bacteria via conjugation.
• Origin:
  • Many resistance genes, such as those coding for β-lactamases, originated in soil bacteria and have spread to pathogenic bacteria over time.

Consequences of Antibiotic Resistance

Hospital and Healthcare Challenges:

• Difficult Treatment:
  • Resistant infections require alternative, often less effective or more toxic treatments.
• Increased Morbidity and Mortality:
  • Leads to longer hospital stays, higher complication rates, and increased death rates.
• Examples:
  • MRSA (Methicillin-Resistant Staphylococcus aureus):
    • Common in hospitals, prisons, and communities.
    • Resistant to multiple drugs, including vancomycin.
  • Multiple Drug-Resistant Infections:
    • Often found in environments with high antibiotic usage, such as hospitals and farms.

Preventing and Managing Antibiotic Resistance

Strategies to Reduce Resistance Development:

1. Appropriate Prescribing:
   • Use antibiotics only when necessary.
   • Avoid prescribing antibiotics for viral infections.
2. Use of Narrow-Spectrum Antibiotics:
   • Target specific bacteria rather than broad-spectrum antibiotics that affect a wide range of bacteria.
3. Complete the Prescribed Course:
   • Ensure patients finish their antibiotic regimen to eliminate all bacteria and prevent resistance.
4. Controlled Access:
   • Restrict over-the-counter sales of antibiotics to reduce misuse.
5. Rotate Antibiotics:
   • Avoid using the same antibiotic repeatedly for the same infection to minimize resistance development.
6. Reduce Agricultural Use:
   • Limit prophylactic antibiotic use in livestock to prevent the spread of resistant bacteria.

Developing New Antibiotics:

• Research:
  • Continuous search for new antibiotics with unique mechanisms of action.
• Modification:
  • Develop semi-synthetic forms of existing antibiotics to overcome resistance.

Testing for Antibiotic Sensitivity

Antibiotic Sensitivity Test:

• Agar Plate Method:
  • Antibiotic-impregnated discs are placed on agar plates cultured with bacteria.
• Inhibition Zones:
  • Clear areas around antibiotic discs indicate bacterial sensitivity.
  • No clear area indicates resistance.

Interpreting Inhibition Zone Diameters:

• Resistant: Diameter ≤ set threshold.
• Sensitive: Diameter ≥ set threshold.

Reducing Antibiotic Resistance:

a. Limiting Antibiotic Use:

• Answer: Reduces unnecessary exposure, decreasing selection pressure for resistant strains.
• b. Changing Prescribed Antibiotics Regularly:
• Answer: Prevents bacteria from repeatedly encountering the same antibiotic, slowing resistance development.

c. Using Combination Therapy:

• Answer: Increases the likelihood that at least one antibiotic will be effective, reducing the survival chances of resistant bacteria.
• Antibiotic Choice for Treating E. coli O157:
• Answer: Choose the antibiotic(s) with inhibition zone diameters equal to or greater than the “sensitive” threshold. Compare each antibiotic’s effectiveness based on the inhibition zones to select the most appropriate treatment.