Antibiotics and Antibiotic Resistance

Learning Outcomes

  • Define antibiotics
  • Explain the mechanisms of action of antibiotics
  • Discuss antibiotic resistance and its mechanisms
  • Explain how to identify antibiotic resistance (Kirby Bauer and E-test)
  • Explain minimum inhibitory concentration (MIC)
  • Explain Therapeutic Index (TI)
  • Discuss the importance of antibiotics from a public health perspective
  • Discuss side effects of fluoroquinolones (including its black box warning)
  • Discuss approaches to slow down antibiotic resistance
  • Describe alternatives to antibiotics

Antimicrobial Jargon

  • Chemotherapeutic drug: Any chemical used to treat, relieve, or prevent disease.
  • Prophylaxis: Using a drug to prevent potential infections.
  • Antimicrobial chemotherapy: Using chemotherapeutic drugs to control infection.
  • Antimicrobials: Any antimicrobial drug regardless of origin.
  • Antibiotics: Substances produced by some microorganisms that inhibit or destroy other microorganisms.
  • Semisynthetic drugs: Drugs modified in the lab after isolation from natural sources.
  • Synthetic drugs: Compounds synthesized entirely in the laboratory.
  • Narrow spectrum antibiotics: Effective against a limited variety of microbes (e.g., mainly gram-positive bacteria).
  • Broad spectrum antibiotics: Effective against a wide variety of microbes (e.g., both gram-positive and gram-negative bacteria).

Historical Context

  • The discovery of penicillin by Alexander Fleming in 1928 marked the start of modern antimicrobial research.
  • First synthetic antimicrobial, sulfanilamide, was discovered by Gerhard Domagk and colleagues from the synthetic dye prontosil.

Antibiotic Functionality

  • Antibiotics: Target bacterial structures (cell wall, ribosomes, plasma membrane) that differ from human cells.
  • They can either:
    • Bactericidal: Kill bacteria.
    • Bacteriostatic: Inhibit bacteria growth, relying on the host's immunity.

Characteristics of Ideal Antimicrobial Drug

  1. Selectively toxic to microbes but not to host cells.
  2. Microbicidal rather than microbiostatic.
  3. Remains potent long enough to act and is not prematurely broken down.
  4. Not subject to the development of resistance.
  5. Complements host defenses.

Antibiotic Mechanisms of Action

  1. Cell wall synthesis inhibition: E.g., penicillins, cephalosporins, which prevent cross-linking of peptidoglycan leading to cell lysis.
  2. Protein synthesis inhibition: Target 30S or 50S ribosomal subunits (e.g., aminoglycosides, tetracyclines).
  3. Disruption of membrane function: E.g., polymyxins disrupt gram-negative membranes.
  4. Nucleic acid synthesis inhibition: E.g., fluoroquinolones affect DNA replication.
  5. Metabolic pathway interference: E.g., sulfonamides block folate synthesis leading to inhibited DNA/RNA production.

Minimum Inhibitory Concentration (MIC) & Testing Methods

  • MIC: The lowest concentration of an antibiotic that inhibits visible growth of a bacterium.
  • Testing methods:
    • Kirby-Bauer Disc Diffusion: Measures the zone of inhibition around antibiotic discs.
    • E-test: Impregnated gradient strips that provide an MIC.

Antibiotic Resistance

  • Resistance mechanisms include:
    • Exclusion from cells: Decreased influx, increased efflux.
    • Modification of targets: Genetic mutations that prevent antibiotic binding.
    • Modification of antibiotics: Chemical degradation by enzymes (e.g., beta-lactamase).
  • The emergence of superbugs due to overuse and misuse of antibiotics is a serious public health issue leading to treatment failures.

Public Health Impact

  • Antibiotic resistance results in significant morbidity and mortality across the globe.
  • Improper antibiotic use contributes to resistance through mechanisms such as selection of resistant strains.

Slowing Down Resistance

  • Strategies:
    • Reduce unnecessary prescriptions.
    • Use antibiotics judiciously in veterinary medicine.
    • Develop alternative therapies like phage therapy and vaccines.
    • Ensure public health measures to control infections and educate on proper antibiotic use.

Summary

  • Antibiotics have revolutionized treatment for infections but the rising threat of resistance due to misuse poses a challenge.
  • Continuous monitoring, responsible prescribing, and research into alternatives are crucial for future public health efforts against infections.