Microbial Growth Control and Antimicrobial Drugs

History of Antimicrobial Agents

  • Definition of Key Terms:

    • Drugs: Chemicals that affect physiology in any manner.
    • Chemotherapeutic agents: Drugs acting against diseases.
    • Antimicrobial agents (antimicrobials): Drugs treating infections.

  • Key Figures in Antimicrobial Development:

    • Paul Ehrlich: Developed the concept of "magic bullets" using arsenic compounds to kill microbes.
    • Alexander Fleming: Discovered penicillin from the mold Penicillium.
    • Gerhard Domagk: Discovered sulfanilamide, the first synthetic antimicrobial.
    • Selman Waksman: Coined the term antibiotics for naturally occurring antimicrobial agents.

  • Types of Antimicrobials:

    • Semisynthetics: Chemically altered antibiotics for improved effectiveness.
    • Synthetics: Fully lab-synthesized antimicrobial substances.
Clinical Considerations in Prescribing Antimicrobial Drugs

  • Ideal Characteristics of an Antimicrobial Agent:

    • Readily available
    • Inexpensive
    • Chemically stable
    • Easily administered
    • Nontoxic and nonallergenic
    • Selectively toxic against wide ranges of pathogens.

  • Spectrum of Action:

    • Narrow-spectrum: Effective against a few organisms.
    • Broad-spectrum: Effective against many organisms, risk of secondary infections and damage to normal flora.
Mechanisms of Antimicrobial Action

  • Selective Toxicity: Crucial for successful chemotherapy targeting pathogens without harming the host.

  • Main Mechanisms:

    • Inhibiting Cell Wall Synthesis:
    • Target organisms unable to maintain cell wall integrity, effective mainly on growing cells.
    • Inhibiting Protein Synthesis:
    • Targeting prokaryotic ribosomes (70S) without affecting eukaryotic ribosomes (80S).
    • Injuring the Plasma Membrane:
    • Certain drugs disrupt membrane function, e.g., using amphotericin B on fungal membranes.
    • Inhibiting Nucleic Acid Synthesis:
    • Blocking replication/transcription using nucleotide analogs.
    • Inhibition of Essential Metabolite Synthesis:
    • Targeting metabolic pathways unique to pathogens, e.g., sulfonamides.
    • Prevention of Virus Attachment, Entry, or Uncoating:
    • New drug targets focusing on antiviral mechanisms.
Evaluating Effectiveness of Antimicrobial Drugs
  • Testing Methods:
    • Diffusion Susceptibility Test (Kirby-Bauer): Measures drug effectiveness by observing inhibition zones.
    • Minimum Inhibitory Concentration (MIC): Determines lowest concentration that prevents growth.
    • Minimum Bactericidal Concentration (MBC): Lowest concentration that kills the bacteria.
Resistance to Antimicrobial Drugs

  • Development of Resistance:

    • Pathogens can be naturally resistant or acquire resistance through mutations or R plasmids.

  • Mechanisms of Resistance:

    • Enzymatic destruction: Producing enzymes that deactivate drugs (e.g., beta-lactamase).
    • Altered uptake: Preventing drug entry into the cell.
    • Target alteration: Changing drug targets to reduce effectiveness.
    • Drug efflux pumps: Actively removing drugs from the cell before they can act.

  • Multiple Resistance and Cross Resistance:

    • Resistant strains may emerge through shared R plasmids, complicating treatment with multiple drugs.
    • Strategies should focus on retarding resistance, such as maintaining high drug concentrations and using combinations of antimicrobials.
Strategies to Overcome Resistance
  • Utilize drugs only when necessary.
  • Develop new variations of existing drugs (second and third-generation).
  • Focus on searching for new antibiotics, semisynthetics, and synthetics to combat resistance.
  • Utilize bacteriocins or design drugs to uniquely inhibit microbial proteins based on molecular structure.