TM

Week 6 S - Antibiotics and Resistance

Learning Outcomes

  • Understanding the mechanisms of key classes of antibiotics

  • Exploring mechanisms of antimicrobial resistance (AMR) for key antibiotics

  • Evaluating considerations behind effective antibiotic utilization

  • Discussing policies and global initiatives to address AMR

Key Classes of Antibiotics

Cell Wall Inhibitors

  • Beta-lactams: Includes Penicillins, Carbapenems, Cephalosporins, Monobactams, and Vancomycin. They inhibit cell wall synthesis, effective against various bacteria.

DNA Replication Inhibitors

  • Quinolones (e.g., Ciprofloxacin, Levofloxacin): Target DNA gyrase crucial for DNA replication. Ciprofloxacin inhibits ligase activity, causing DNA damage and cell death.

    • Resistance: Can arise from single nucleotide polymorphisms (SNPs) within the quinolone resistance determining region (QRDR) affecting drug binding.

Transcription Inhibitors

  • Rifampin: Inhibits RNA polymerase, preventing transcription of bacterial DNA into RNA. Effective against some bacterial infections.

Protein Synthesis Inhibitors

  • Macrolides (e.g., Erythromycin, Chloramphenicol): Block protein synthesis in ribosomes (50S and 30S). Effective against various pathogens.

  • Tetracyclines (e.g., Doxycycline): Specifically prevent bacterial growth by inhibiting protein synthesis and are broad-spectrum.

Folic Acid Biosynthesis Inhibitors

  • Sulfonamides and Trimethoprim: Act synergistically to inhibit pathways necessary for bacterial growth, useful for treating a wide range of infections.

Resistance Mechanisms

  • Single Nucleotide Polymorphisms (SNPs): Small mutations can lead to high-level resistance in certain antibiotics like quinolones.

  • Gene Transfer: Horizontal gene transfer (HGT) enables movement of AMR genes between bacterial strains and species, leading to multi-drug resistant strains (MDR).

Considerations for Effective Antibiotic Use

  • Choice of antibiotic based on:

    • Pathogen: Identifying specific bacteria causing infection.

    • Infection Site: The location of infection can influence drug effectiveness.

    • Patient Factors: Individual patient health, allergies, and previous antibiotic use.

    • Resistance: Awareness of local resistance patterns.

    • Side Effects: Monitoring adverse reactions to antibiotics during treatment.

Global Initiatives and Policies

  • One Health Approach: Integrating health across humans, animals, and the environment to combat AMR through reduced antibiotic use in livestock.

  • Antimicrobial Stewardship: Organizational efforts to promote judicious use of antibiotics, monitor their use and resistance trends, and guide treatment decisions.

  • WHO Priority List: A guiding document that identifies priority pathogens and informs research and policy initiatives to address AMR.

Summary

  • Antibiotics remain crucial in modern healthcare but face significant threats from AMR.

    • Awareness of mechanisms, resistance, and global initiatives is essential for future effectiveness.