15 micro

Antimicrobial Drugs: Introduction and Historical Context

Discovery and Development of Antimicrobial Drugs

Antimicrobial drugs are therapeutic compounds that kill or inhibit the growth of microbes. Their development revolutionized medicine, drastically reducing deaths from infectious diseases.

• Alexander Fleming (1928): Discovered penicillin from the mold Penicillium after observing inhibition of Staphylococcus aureus growth near the mold on a culture plate.

• Streptomycin: Isolated from Streptomyces griseus, a soil bacterium, and effective against tuberculosis.

• Before antimicrobial drugs, infections were a leading cause of death, especially in war-related injuries.

Key Terms:

• Antibacterial drugs: Treat bacterial infections.

• Antiviral drugs: Target viral infections.

• Antifungal drugs: Target fungal infections.

• Antiparasitic drugs: Treat protozoan and helminth (worm) infections.

Spectrum and Mechanisms of Antimicrobial Action

Spectrum of Activity

Antibacterial drugs are classified by their spectrum of activity, which determines the range of microbes they affect.

• Broad-spectrum drugs: Effective against both Gram-positive and Gram-negative bacteria. Useful when the pathogen is unknown or mixed infections are suspected.

• Narrow-spectrum drugs: Target a limited range of bacteria, preferred to minimize disruption to normal microbiota.

• Empiric therapy: Initiated before pathogen identification, often using broad-spectrum drugs.

Mechanisms of Action

• Bacteriostatic drugs: Prevent bacteria from growing by targeting protein synthesis and metabolic pathways.

• Bactericidal drugs: Kill bacteria by targeting cell walls, cell membranes, or nucleic acids.

Factors affecting drug action: Pathogen type, dose, regimen length, pathogen load, and route of administration.

Types of Antimicrobial Compounds

Natural, Synthetic, and Semisynthetic Antimicrobials

• Antibiotics: Naturally occurring antimicrobial compounds (e.g., penicillin, streptomycin).

• Synthetic antimicrobials: Manufactured by chemical processes (e.g., sulfa drugs).

• Semisynthetic antimicrobials: Chemically modified natural antibiotics to enhance properties (e.g., ampicillin, amoxicillin).

Drug Modifications and Generations

• First-generation drugs: Result from initial chemical modification.

• Second-generation drugs: Further modifications, often with expanded spectrum, increased stability, or resistance circumvention.

• Later generations may offer improved activity against resistant pathogens.

Example: Ampicillin and amoxicillin are penicillin derivatives with broader activity due to added chemical groups.

Drug Safety and Toxicity

Therapeutic Index and Selective Toxicity

Drug safety is assessed by balancing efficacy and risk of side effects.

• Therapeutic index: Ratio of maximum tolerated/safe dose to minimum effective/therapeutic dose.

$\text{Therapeutic Index} = \frac{\text{Maximum safe dose}}{\text{Minimum effective dose}}$

• High therapeutic index = safer drug.

• Low therapeutic index = higher risk, may be acceptable for life-threatening infections.

Therapeutic Drug Monitoring (TDM)

• Involves measuring drug concentrations in blood and monitoring patient parameters to ensure safety and efficacy.

Toxicity Considerations

• Nephrotoxic drugs: Can damage kidneys (e.g., aminoglycosides).

• Hepatotoxic drugs: Can damage liver.

• Drug interactions and contraindications must be considered in therapy and development.

Summary Table: Types of Antimicrobial Drugs

Type	Target Pathogen	Example
Antibacterial	Bacteria	Penicillin, Streptomycin
Antiviral	Viruses	Acyclovir
Antifungal	Fungi	Amphotericin B
Antiparasitic	Protozoa, Helminths	Metronidazole

Key Definitions and Concepts

• Selective toxicity: Ability of a drug to target microbes without harming host cells.

• Drug half-life: Time required for half the drug to be eliminated from the body.

• Contraindication: Condition or factor that serves as a reason to withhold a certain medical treatment.

Additional info:

• Antimicrobial resistance and drug development challenges are covered in later sections of the chapter.

• Clinical application requires consideration of drug spectrum, toxicity, and patient-specific factors.