Antimicrobial Chemotherapy: General principles, Types of Antimicrobial Agents according to their Mechanism of Action, Adverse reaction
Here are short notes on Antimicrobial Chemotherapy, drawing from the provided sources:
General Principles
- Antimicrobial chemotherapy involves the treatment of infectious diseases using antimicrobial agents.
- Antimicrobial agents include antibiotics (natural substances produced by certain microorganisms) and chemotherapeutic agents (chemically synthesized).
- Often, all antimicrobial agents are colloquially called antibiotics.
- A key principle is selective toxicity, meaning the agent must be highly effective against the microbe but have minimal or no toxicity to humans.
- The antibacterial spectrum refers to the range of activity of an antimicrobial against bacteria. This can be broad spectrum (effective against a wide variety of Gram-positive and Gram-negative bacteria) or narrow spectrum (active against a limited variety of bacteria).
- Antimicrobial activity can be bacteriostatic (inhibits bacterial growth reversibly) or bactericidal (kills bacteria irreversibly).
- The therapeutic index is the ratio of maximal tolerable dose to minimal therapeutic dose.
- Some substances exhibit a postantibiotic effect (PAE), where bacterial cells not killed require a recovery phase before reproducing after the agent is removed.
Types of Antimicrobial Agents based on Mechanism of Action
Antibiotics are often classified based on how they inhibit bacterial growth.
- Inhibitors of Cell Wall Synthesis: These target the bacterial cell wall, often specifically peptidoglycan formation, leading to cell lysis.
- β-lactams: Include penicillins, carbapenems, cephalosporins, and monobactams. They bind to penicillin-binding proteins (PBPs).
- Glycopeptides: E.g., vancomycin, teicoplanin. They disrupt cell wall peptidoglycan synthesis by binding to D-alanyl-D-alanine.
- Bacitracin: Inhibits the incorporation of peptidoglycan subunits; primarily used topically.
- Fosfomycin: Blocks murein biosynthesis; rapid resistance development, used in combination.
- Inhibitors of Protein Synthesis: These target the bacterial ribosome (70S, composed of 30S and 50S subunits).
- Aminoglycosides: E.g., streptomycin, gentamicin, amikacin. Bind to the 30S ribosomal subunit. Often bactericidal.
- Tetracyclines: E.g., tetracycline, doxycycline. Bind reversibly to the 30S ribosomal subunit, blocking tRNA binding. Often bacteriostatic.
- Macrolides: E.g., erythromycin, clarithromycin, azithromycin. Bind to the 50S ribosomal subunit. Often bacteriostatic.
- Chloramphenicol: Binds to the 50S ribosomal subunit, blocking polypeptide elongation. Broad-spectrum, often bacteriostatic.
- Lincosamides: E.g., clindamycin. Bind to the 50S ribosomal subunit. Often bacteriostatic.
- Mupirocin: Inhibits bacterial isoleucyl-tRNA synthetase.
- Streptogramins: E.g., quinupristin/dalfopristin. Bind to the 50S ribosomal subunit.
- Inhibitors of Nucleic Acid Synthesis: These interfere with DNA or RNA replication or synthesis.
- Fluoroquinolones (Quinolones): Inhibit DNA replication by targeting DNA gyrase and topoisomerases. Often bactericidal.
- Rifamycins: E.g., rifampicin. Inhibit bacterial RNA polymerase, preventing RNA synthesis. Often bactericidal.
- Antimetabolites: These interfere with essential metabolic pathways.