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Antimicrobial Drugs

Chapter 11: Antimicrobial Drugs

1. Introduction

  • Instructor: Dr. Danielle Marcelle Ward, PhD
    • Departments: Anatomy & Physiology, Microbiology, English
    • Institution: Jersey College School of Nursing
    • Contact Information: Email - dward@jerseycollege.com

2. Learning Goals

  • Discuss the general goal of antimicrobial drug actions.
  • Describe the five basic categories of mechanisms used by antimicrobial drugs.
  • Explain the various spectra of activity for antimicrobial drugs.
  • Name and describe factors that need to be considered in selecting an antimicrobial drug.
  • Explain the therapeutic index and discuss possible side effects associated with antimicrobial therapy.

3. Mechanisms of Antimicrobial Action

  • Goal of Antimicrobial Actions: To interfere with the metabolism or structure of the organism so that it cannot survive or reproduce.
    • Achieved in two ways:
    • Microbicidal
      • Kills microbes.
      • Can also kill normal flora—potential risk for superinfection.
    • Microbiostatic
      • Reversibly inhibits growth; once removed, microbes can recover and grow again.
  • Factors Influencing Effectiveness:
    • Concentration of the agent
    • Type of microbe targeted
    • Host’s immune system

4. Mechanisms of Action

4.1 Inhibition of Cell Wall Synthesis

  • Causes weakness of peptidoglycan layer, making it vulnerable to lysis.
  • Agents:
    • Penicillin
    • Cephalosporins

4.2 Inhibition of Protein Synthesis

  • Disruption of translation at the ribosome.
  • Eukaryotic ribosomes are not affected, which protects human cells from these agents.

4.3 Inhibition of Nucleic Acid Synthesis

  • Disruption of DNA and RNA synthesis.
  • Complexity of metabolic processes leads to disruption at multiple points.
  • Includes:
    • Disruption of synthesis of nucleotide components
    • Inhibition of DNA replication
    • Interference with RNA transcription
    • End result: competitive inhibition

4.4 Disruption of Plasma Membrane

  • Affects the transport in/out of the cell and weakens the cell's physical integrity.
  • Can affect both prokaryotic and eukaryotic cells.

4.5 Inhibition of Metabolic Pathways

  • Disrupts numerous cellular metabolic processes and enzyme activity/production, as well as essential metabolic compounds.

5. Characteristics of Antimicrobial Agents

  • Spectrum of Action: The variety of microbes affected by the antimicrobial agent.
  • Selective Toxicity: Ideally should kill only pathogens without significant damage to the host.
  • Microbicidal vs. Microbiostatic:
    • Antimicrobial drugs killing microorganisms are termed bactericidal.
    • Those preventing growth are termed bacteriostatic.
  • Delivery to Infection Site:
    • Efficacy and potential barriers to delivery (body linings, blood-brain barrier).
    • Influenced by solubility and concentration.
  • Time of Activity:
    • Duration of effectiveness, concentration versus time, and potential for resistance development.
  • Stability and Shelf Life: Longer shelf life enhances availability.
  • Affordability and Availability: Important for patient access to treatment.

6. Spectrum of Action

  • Broad Spectrum: Effective against a large variety of microorganisms.
  • Narrow Spectrum: Effective against a relatively small range of organisms, minimizing damage to normal flora.
  • Medium Spectrum: Effective against some gram-positive and gram-negative bacteria, but not all.

7. Antimicrobial Resistance

  • Development of Resistance:
    • Ideally, there should be no resistance.
    • Resistance arises from genetic mutations or acquisition of resistance genes by microbes through:
    • Conjugation
    • Transduction
    • Transformation
  • Natural selection fosters the development of drug-resistant forms of microbes in nature, labs, and medical environments.

7.1 Mechanisms of Resistance

  • Changes in:
    • Membrane permeability
    • Drug elimination processes
    • Target receptor sites
    • Metabolic pathways
    • Previously inhibited enzymes
    • Development of defensive enzymes

7.2 Multiple Resistances

  • A global problem primarily arising from improper use of prescribed antibiotics.
  • Often develops in healthcare environments leading to the emergence of “superbugs.”
  • Cross-resistance: A phenomenon where resistance to one antimicrobial drug confers resistance to others.

7.3 Preventing Drug Resistance

  • Handwashing and elimination of unwarranted antibiotic use.
  • Targeting a narrow range of microbes.
  • Using drug combinations (synergism) and isolating facilities with ongoing infections.
  • Awareness of current data regarding resistance.
  • Adherence to prescription guidelines, including disposing of leftover medications and not sharing prescriptions.
  • Use antimicrobial soaps judiciously to avoid disruption of normal flora.

8. Antibacterial Agents

8.1 Types of Antibacterial Agents

  • Natural Antibiotics: Produced by microorganisms.
  • Semisynthetic Antibiotics: Chemically modified natural antibiotics.
  • Synthetic Drugs: Laboratory-produced antibiotics.

8.2 Examples of Antibacterial Agents

  • Penicillins:
    • Produced by Penicillium chrysogenum (fungus).
    • First widely used antibiotic; semisynthetic varieties include ampicillin and methicillin.
  • Cephalosporins: Structurally similar to penicillins, often given to patients with penicillin allergies.
    • Multiple generations exist, each with a broader spectrum of activity.
  • Tetracyclines:
    • Broad-spectrum antibiotics (natural and semisynthetic) that inhibit protein synthesis.
  • Aminoglycosides: Naturally produced, bactericidal agents with significant toxicity and side effects.
  • Macrolides:
    • Natural (e.g., erythromycin) and semisynthetic; broad spectrum with bacteriostatic properties and relatively low toxicity.
  • Chloramphenicol:
    • Very potent, broad-spectrum bacteriostatic agent with high toxicity, used in restricted cases.
  • Lefamulin:
    • Novel semi-synthetic antibiotic inhibiting a specific bacterial protein essential for bacterial growth; primarily treats community-acquired bacterial pneumonia.
  • Bacillus Antibiotics:
    • Relatively narrow spectrum agents, including bacitracin and polymyxins, generally used for surface infections.

9. Antiviral Agents

  • Challenges in Developing Antivirals: Targeting viral life cycles without harming host cells is critical.
    • Targets include:
    • Preventing penetration
    • Blocking transcription/translation
    • Preventing maturation of the virus, with limitations as most drugs have little effect on extracellular viruses.

9.1 Characteristics of Antiviral Agents

  • Purine and Pyrimidine Analogs:
    • Example: Acyclovir, an analogue of guanine, less toxic than other options.
  • Amantadine: Prevents influenza A, with 50% to 80% effectiveness.
  • Azidothymidine (AZT): Primarily used in AIDS treatment, often combined with other antivirals as a “cocktail.”
  • Interferons: Produced by virally infected cells, inducing the production of antiviral agents in neighboring cells.

10. Antifungal Agents

10.1 Characteristics

  • Synthetic Azoles: Broad-spectrum agents used for superficial infections like athlete's foot and vaginal candidiasis; some also treat systemic infections.
  • Flucytosine: Broad-spectrum, used for systemic infections and cutaneous mycoses.
  • Macrolide Polyene Antibiotics: Used for systemic mycoses.
  • Griseofulvin: Narrow-spectrum agent primarily for localized dermatophyte infections.
  • Echinocandins: Used for systemic infections and as prophylaxis against the cyst form of Pneumocystis carinii.

11. Antiprotozoan Agents

11.1 Characteristics

  • Chloroquine and Primaquine: Synthetic drugs derived from quinine used to treat Plasmodium infections (malaria).
  • Metronidazole: Treats Trichomonas vaginal infections and gastrointestinal infections caused by Giardia.
  • Pyrimethamine: Prevents and treats malaria when used with sulfanilamide; also treats toxoplasmosis.
  • Quinine: Natural extract from cinchona trees, historically used to treat malaria.

12. Antihelminthic Agents

  • Overview: Treatment of helminths is challenging due to their eukaryotic nature.
  • Common Agents:
    • Niclosamide
    • Mebendazole
    • Piperazine
    • Ivermectin

Note: All drugs have the potential to cause side effects; monitoring patient response and adjusting treatment as necessary is crucial.