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.