Overview
This lecture covers antimicrobial drugs, focusing on key terms, mechanisms of action, drug selection, resistance, and recent advances in alternative therapies.
Key Terms in Antimicrobial Drugs
- Chemotherapy is the treatment of disease with chemical substances (not limited to cancer).
- Antibiotics are antimicrobial agents usually produced by bacteria or fungi to inhibit competitors.
- Selective toxicity refers to drugs that harm microbes with minimal damage to the host.
- Broad-spectrum antibiotics target a wide variety of organisms; narrow-spectrum are selective.
Desirable Qualities & Classifications
- An ideal antimicrobial drug is selectively toxic, stable, easy to administer, effective at low dose, and does not cause resistance easily.
- Broad-spectrum antibiotics can disrupt normal flora, causing side effects like superinfections and yeast infections.
- Narrow-spectrum antibiotics are more targeted but require knowledge of the specific causative organism.
Mechanisms of Action of Antimicrobial Drugs
- Drugs can inhibit cell wall synthesis (e.g., penicillin), protein synthesis (e.g., tetracycline), nucleic acid synthesis (e.g., ciprofloxacin), plasma membrane function (e.g., polymyxin B), or essential metabolic pathways (e.g., sulfa drugs).
- Bactericidal drugs kill microbes; bacteriostatic drugs inhibit their growth.
Selective Toxicity and Challenges
- Cell wall inhibitors are selectively toxic because human cells lack peptidoglycan.
- Protein synthesis inhibitors target bacterial 70S ribosomes (humans have 80S, except in mitochondria).
- Some mechanisms, like plasma membrane disruption, are less selectively toxic due to similarities with host cells.
- Treating viruses, protozoa, fungi, and helminths is harder due to their similarity to host cells or intracellular lifestyle.
Drug Resistance & Evolution
- Common resistance mechanisms: reduced permeability, efflux pumps, altered targets, and antibiotic inactivation.
- Resistance arises via vertical (mutation) or horizontal (gene transfer: transformation, transduction, conjugation) gene transfer.
- Misuse and incomplete antibiotic courses promote selection of resistant strains.
Testing and Therapy Guidance
- Identify infecting microorganism, test susceptibility (Kirby Bauer, E-test for MIC), and consider patient condition before treatment.
- Therapeutic index measures a drug's safety margin.
Alternative Approaches & New Therapies
- Bacteriophage therapy, anti-quorum sensing drugs, fecal microbiota transplant, antibody therapy, and use of predatory bacteria are emerging alternatives.
Key Terms & Definitions
- Chemotherapy — treatment of disease with chemicals.
- Antibiotic — antimicrobial agent from bacteria/fungi.
- Selective toxicity — drug harms microbe, not host.
- Bactericidal — kills bacteria.
- Bacteriostatic — inhibits bacterial growth.
- Beta-lactam ring — core chemical structure in penicillins/cephalosporins.
- MIC — minimum inhibitory concentration.
Action Items / Next Steps
- Review the five drug mechanisms and one example for each.
- Understand the difference between broad and narrow-spectrum drugs.
- Know resistance mechanisms and how to prevent their spread.
- Complete class assignments as posted on Canvas.