Lecture Notes on Antimicrobials

Introduction to Antimicrobials

• Chapter 14 focuses on antimicrobials and their significance in treating infectious diseases.
• Key areas of discussion:
  • Important terminologies in antimicrobials.
  • Spectrum of antimicrobial activity (broad vs narrow spectrum).
  • Different types of antimicrobials: antibiotics, antivirals, antiprotozoans, and antihelminths.
  • Modes of antimicrobial resistance and evaluating antimicrobial effectiveness.

Historical Context

• Graph comparing deaths from infectious diseases in 1900 vs a recent year.
  • Significant decline in infectious disease mortality due to antimicrobial agents and vaccines.
  • Factors contributing to infectious disease reduction include:
  • Introduction of antibiotics, antivirals, antifungals.
  • Increased vaccination rates.
  • Enhanced sanitation and medical interventions.
  • Improved public health education.
  • Advances in technology and rapid diagnostic methods.

Definitions and Key Terms

• Chemotherapy: Treatment of diseases with chemical agents, broadly applicable beyond cancer treatment.
• Antimicrobials: Agents specifically used to treat infections caused by microbes (bacteria, viruses, fungi, protozoa).
• Antibiotics: Substances that inhibit or kill bacteria, not effective against viruses.
  • True antibiotics: Derived from microorganisms (e.g., penicillin from Penicillium).
  • Synthetic antibiotics: Chemically produced in laboratories (e.g., sulfa drugs).
  • Semi-synthetic antibiotics: Modified natural antibiotics (e.g., amoxicillin).

Spectrum of Activity

• Spectrum: Range of microbes affected by antibiotics.
  • Broad spectrum: Effective against a wide array of bacteria (e.g., tetracyclines, amoxicillin).
  • Narrow spectrum: Targets specific groups of bacteria (e.g., isoniazid for mycobacteria).

Selective Toxicity

• Ability to kill the microbe without harming the host.
  • Toxic dosage level: Concentration harming the host.
  • Therapeutic dosage level: Concentration effective against pathogens without harming the host.

Routes of Administration

• Methods to introduce antimicrobials into the body:
  • Oral: Usually slower onset but longer duration.
  • Intramuscular (IM): Faster peak concentration but shorter duration.
  • Intravenous (IV): Rapid action with varying duration depending on drug.

Mechanisms of Action of Antibiotics

1. Inhibition of Cell Wall Synthesis: Targeting bacterial cell walls (selective toxicity).
   • Examples: Penicillins (natural and semi-synthetic), cephalosporins.
2. Disruption of Cell Membrane Function: Compromise bacterial membranes leading to loss of cellular contents.
   • Example: Polymyxin B.
3. Inhibition of Protein Synthesis: Targeting bacterial ribosomes.
   • Examples: Aminoglycosides (e.g., streptomycin), tetracyclines, macrolides.
4. Inhibition of Nucleic Acid Synthesis: Preventing DNA/RNA synthesis.
   • Examples: Fluoroquinolones (e.g., ciprofloxacin), rifamycins (e.g., rifampin).
5. Inhibitors of Metabolic Pathways: Mimicking metabolites in biosynthetic pathways.
   • Example: Sulfonamides (e.g., Bactrim).

Antifungals

• Antifungals target fungi which are eukaryotic and share similarities with human cells, making selective toxicity challenging.
  • Examples: Amphotericin B (systemic infections), azoles (clotrimazole, fluconazole - for superficial and systemic fungal infections).

Antivirals

• Antivirals are limited due to the need for targeting within human cells.
  • Examples:
  • Tamiflu: Inhibits neuraminidase in influenza.
  • Acyclovir: Inhibits viral DNA synthesis.
  • Interferon: Natural cell-produced antiviral.
  • AZT: Targets reverse transcriptase in HIV.

Antiprotozoans and Antihelminths

• Antiprotozoans: Target protozoan infections (e.g., chloroquine for malaria).
• Antihelminths: Target helminthic infections (e.g., ivermectin for parasitic worms).

Antimicrobial Resistance

• Mechanisms of resistance include:
  1. Efflux Pumps: Remove antibiotic compounds from cells.
  2. Blocked Penetration: Modification of cell membranes to prevent drug entry.
  3. Inactivation by Enzymes: E.g., beta-lactamase breaks down beta-lactam antibiotics.
  4. Target Modification: Changes in target sites preventing drug binding.
  5. Target Overproduction: Overexpression of targets to outcompete drugs.
  6. Enzymatic Bypass: Alternative metabolic pathways circumventing drug action.

Evaluating Antimicrobial Effectiveness

• Kirby-Bauer Disk Diffusion: A test determining susceptibility based on the zone of inhibition.
• Dilution Method: Determines Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC).
• E-Tests: Combine aspects of Kirby-Bauer and MIC measurements for precise evaluations.

Conclusion

• Understanding different treatments and mechanisms of action for antimicrobials is crucial for effective therapy and addressing bacterial resistance.