Antibiotics

• Anti-microbial agents


  Naturally occurring or chemically synthesised substances intended to be toxic for the pathogenic organisms but harmless to the host, e.g. antibiotics, antifungals, antivirals, antiparasitics etc
• Antibiotic


  Natural substance, or derivative of a natural substance, which when taken in small doses, will either kill or prevent the growth of bacteria, but not seriously harm the person taking it
• What is the role of anti-microbial agents?

  Help the immune system to irradicate infections. Sometimes they work in synergy while other times they help the immune system to fight infection
• Classification of Antibiotics


  • Mode of action
  • Chemical structure
  • Spectrum of activity
  • Effect on organism
• Inhibition of cell wall synthesis


  • e.g. β lactams, Vancomycin

  
• Disruption of cell membrane function


  • e.g. nystatin, Amphotericin B
• Inhibition of protein synthesis

  • e.g. aminoglycosides, tetracyclines, chloramphenicol, lincosamides
• Inhibition of nucleic acid synthesis

  • e.g. metronidazole, Quinolones (Nalidixic acid, Ciprofloxacin)
• Inhibition of metabolic pathways


  • e.g. sulfonamides, trimethoprim
• Synthesis of Peptidoglycan Cell Wall

  1. Bacteria increase their size following binary fission and send a signal to a bacterial enzyme called autolysin

  2. Autolysin breaks the glycosidic bonds between the peptidoglycan monomers and the peptide cross-bridges

  3. New peptidoglycan monomers are inserted

  4. Transglycosidase enzyme catalyses the formation of the glycosidic bonds

  5. Transpeptidase enzymes reform the peptide crosslink between the two rows of the peptidoglycan monomers

  
• Broad spectrum of activity

  Antimicrobial drug effective against a large variety of microbes (both Gram +ve and -ve), but a disadvantage is that there's a high likelihood of destroying friendly bacteria of patient's normal microbial flora
• Narrow spectrum of activity

  Antimicrobial drug effective against only a relatively small subset of bacteria (either Gram +ve or -ve)
• Bactericidal


  Antibiotic interacts with bacteria, resulting in an irreversible disruption or binding, leading to cell death
• Bacteriostatic


  Antibiotic binds reversibly to the bacteria and slows down the growth of bacteria, giving enough time for the immune system to resolve the infection

  
• Penicillin


  Discovered accidentally by Alexander Fleming in 1928 and is produced by Penicillium fungi. Works by inhibiting the cell wall synthesis through binding and inhibiting transpeptidase enzymes involved in transpeptidation of peptidoglycan. Only works on Gram +ve bacteria, not Gram -ve ones as it can't penetrate the outer membrane of Gram -ve bacteria

  
• Disruption of Cell Membrane Function

  • Antibiotics damage the cytoplasmic membrane, increasing the permeability of bacteria by disorganizing the structure or inhibiting the function of bacterial membranes, causing destruction of the function of the membrane. The three types are polymyxins, nystatin and amphotericin B

  
• Inhibitors of Protein Synthesis

  • Antimicrobials that bind to 30S ribosomal subunit: Aminoglycosides (bactericidal), Tetracyclines (bacteriostatic)

  Antimicrobials that bind to 50S ribosomal subunit: Chloramphenicol, clindamycin (bacteriostatic), Macrolides (bacteriostatic)
• Inhibitors of nucleic acid synthesis and function

  • Inhibitors of RNA synthesis and function, e.g. Rifampicin (bactericidal)

  Inhibitors of DNA synthesis and function, e.g. Quinolones such as Nalidixic acid, Ciprofloxacin (Bactericidal)

  Metronidazole inhibits anaerobic bacteria and protozoa
• Inhibition of metabolic pathways

  • Sulphonamides (Bacteriostatic), e.g. Co-trimoxazole, Trimethoprim (Bacteriostatic)
• Empiric antibiotic therapy


  Infecting organism(s) is not yet identified so an antibiotic with a more broad spectrum is used at first to slow down the infection. This gives enough time to identify the bacteria
• Definitive antibiotic therapy


  Organism(s) identified and specific therapy chosen, meaning an antibiotic with a more "narrow" spectrum is used
• Prophylactic or preventative antibiotic therapy


  Prevents an initial infection or its recurrence after infection
• Antibiotic resistance


  Bacteria are said to be resistant to an antibiotic if the maximum level of that antibiotic that can be tolerated by the host and does not halt their growth