Week 4

• What was the basis for early treatments of infections?

  Natural remedies and toxic substances
• Which plant extract was discovered to be effective against malaria?

  Quinine
• What was mercury used to treat?

  Syphilis
• What oil was used to treat leprosy?

  Chaulmoogra oil
• Who introduced carbolic acid for disinfecting wounds?

  Joseph Lister
• What replaced carbolic acid for wound disinfection?

  Sulfa drugs
• What are the different categories of antimicrobials?

  • Bactericidal: kill bacteria
  • Bacteriostatic: inhibit bacterial growth
  • Sporicidal: kill bacterial spores
  • Virucidal: kill viruses
  • Antiprotozoal: kill protozoa
  • Antifungal: kill fungi
  • Anthelmintic: kill parasitic worms
• Why has triclosan been banned in some countries?

  Due to concerns about antibiotic resistance and hormone disruption
• What are the principles of selective toxicity in antibiotics?

  • Target bacterial cells without harming mammalian cells
  • Concentrate in bacterial cells rather than host cells
  • Effectiveness varies based on meeting these criteria
  • Side effects differ between specific antibiotic agents
• What is the role of bactericidal antibiotics?

  They kill bacteria
• What do bacteriostatic antibiotics do?

  They inhibit bacterial growth
• How can bacteriostatic antibiotics treat infections?

  By preventing bacterial growth, allowing the immune system to eliminate the infection
• Which species is used for the production of penicillin?

  Penicillium chrysogenum
• What was the original species discovered by Fleming that was not effective for pharmaceutical use?

  Penicillium rubens
• Who was involved in the discovery and development of penicillin?

  Alexander Fleming, Howard Florey, Ernest Chain, and Norman Heatley
• What year did the Nobel Prize for medicine go to the discoverers of penicillin?

  1945
• Who discovered streptomycin?

  Selman Waksman
• What is a serendipitous discovery?

  A chance discovery
• Why are there many antibiotics that act on the cell wall?

  Because the cell wall is a unique structure found only in bacteria

  
• Why are there few antibiotics that act on nucleic acids?

  Because nucleic acids are similar in structure to human cells

  
• How can infection be managed by addressing stages 1 and 2 of the infection process?

  • Preventing attachment: physical barriers like condoms or vaccines
  • Inhibiting penetration: drugs that interfere with bacterial penetration mechanisms
  • Cell wall/membrane: antibiotics like beta-lactams disrupt the cell wall
  • Nucleic acid: quinolones and metronidazole interfere with DNA replication
  • Protein synthesis: antibiotics inhibit protein synthesis
  • Anti-metabolites: sulfonamides and trimethoprim disrupt metabolic pathways

  
• What is peptidoglycan composed of?

  1. acetylmuramic acid (NAM) and N-acetylglucosamine (NAG)

  
• What is the role of transpeptidase enzymes in bacterial cell walls?

  They catalyze the formation of peptide cross-links between NAM-NAG monomers

  
• How does vancomycin inhibit bacterial cell wall synthesis?

  By binding to NAM-NAG monomers and preventing transpeptidase enzymes from accessing their target

  
• What do autolysins do in the presence of vancomycin?

  They break peptide bonds but cannot form new ones, leading to cell wall weakening

  
• What is the mechanism of action of glycopeptides?

  1. Bind to the intact peptidoglycan layer
  2. Transpeptidase enzymes bind NAM-NAG monomers
  3. Vancomycin binds NAM-NAG monomers, inhibiting transpeptidase
  4. Autolysins break peptide bonds, but no new bonds are formed

  
• How do glycopeptides prevent cell wall synthesis?

  By binding to the D-Ala-D-Ala terminus of the peptidoglycan precursor

  
• Why is vancomycin regarded as an antibiotic of last resort?

  Due to the increasing problem of bacterial resistance

  
• What are examples of bacteria that have developed resistance to vancomycin?

  Vancomycin-resistant enterococci (VRE) and VISA
• How do bacteria modify their cell wall precursors to resist vancomycin?

  By replacing D-alanine with D-lactate

  
• What is the mechanism of action of beta-lactam antibiotics?

  • Target PBPs essential for bacterial cell wall synthesis
  • Inhibit cross-link formation in peptidoglycan
  • Lead to cell lysis
  • Bactericidal, killing actively growing bacteria

  
• What do beta-lactamase enzymes do?

  They hydrolyze the beta-lactam ring, rendering antibiotics inactive

  
• What are the different classes of beta-lactamase enzymes?

  • Penicillinases
  • Extended-spectrum beta-lactamases (ESBLs)
  • Metallo-beta-lactamases
• What is the role of beta-lactamase inhibitors?

  They bind to beta-lactamase enzymes, preventing them from inactivating beta-lactam antibiotics

  
• What is clavulanic acid used for?

  As a beta-lactamase inhibitor combined with amoxicillin

  
• What infections does penicillin remain effective for treating?

  Streptococcal infections, Neisseria meningitidis infections, and syphilis
• What bacterial genus is most commonly associated with endocarditis?

  Streptococcus
• How do broad-spectrum antibiotics differ from specialist antibiotics?

  Broad-spectrum antibiotics have a wider range of activity
• What is the mechanism of action of polymyxins?

  They disrupt bacterial cell membranes, leading to cell death

  
• What is the risk associated with colistin in patients with impaired renal function?

  Increased risk of nephrotoxicity and neurotoxicity