Antibiotics

• Define Antibiotic?

  ANTIBIOTIC – a product produced by a microorganism or a similar substance produced wholly or partially by chemical synthesis, which in low concentrations, inhibits the growth of other microorganisms.
• What do antibacterial drugs inhibit?

  Antibacterial drugs inhibit;

  1. Cell wall synthesis
  2. Protein synthesis
  3. Nucleic acid synthesis
  4. Essential metabolite synthesis
  5. Cause injury to plasma membrane
• Bacteriostatic antibiotic

  BACTERIOSTATIC – inhibit the growth of microorganisms (Chloramphenicol)
• Bactericidal

  BACTERICIDAL – kill microorganisms (Penicillin)
• Beta Lactams


  Irreversibly inhibit enzymes involved in the cell wall synthesis (transpeptidases) which mediate the formation of peptide bridges between adjacent strands of peptidoglycan
• Beta Lactams


  • Only effective against rapidly growing organisms that synthesise peptidoglycan
  • Some bacteria produce beta-lactamase
• Penicillins


  Acid labile – easily destroyed in acidic environment
• Penicillins active against G+ bacteria

  • Benzylpenicillin
  • Phenoxymethylpenicillin
• Broad-spectrum penicillins against G-

  • Amoxicillin
  • Ampicillin
• Penicillins are ineffective against penicillinase-producing bacteria e.g. S.aureus, 50% of E.coli
• Penicillinase-resistant penicillins


  • Flucloxacillin
• Anti-staphylococcal penicillins


  • Methicillin (rarely used due to toxicity)
  • Nafcillin
  • Oxacillin
  • Cloxacillin
• Cephalosporins


  Class of antibiotics
• Cephalosporin generations


  • 1st Generation
  • 2nd Generation
  • 3rd Generation
  • 4th Generation
• 1st Generation Cephalosporins


  • Cefazolin - staph, non-enterococcal strep, prophylactic, cellulitis, folliculitis
  • Limitations - respiratory tract infections, animal bites and colonic surgeries
• 2nd Generation Cephalosporins


  • Cefuroxime - respiratory infections (S. pneumoniae, H. influenzae), meningitis due to pneumococcus, H. influenza and N. meningitides
  • Limitations - enteric organisms/abdominal anaerobes
  • Cefoxitin/Cefotetan - intra-abdominal infections, limitations - staph and G+
• 3rd Generation Cephalosporins


  • Cefotaxime and Ceftriaxone - staph and non-enterococcal strep, broad for G- and oral anaerobes, CNS, pulmonary, endovascular, GI infections, sinusitis, otitis
  • Doesn't cover Pseudomonas, limited utility in treating biliary tree infections
  • Ceftazidime - G- including Pseudomonas, febrile neutropenia, CNS infections but reduced activity against G+ and oral anaerobe
• 4th Generation Cephalosporins


  • Cefepime and Cefpriome - aerobic G- (Enterobacter, Klebsiella, Pseudomonas), G+ (Strep, MSSA), used in neutropenic fever and CNS infctions
• Beta-lactamase inhibitors


  • Clavulanic acid
  • Tazobactam
• Piperacillin/tazobactam


  Anti-pseudonomas antimicrobials
• Ticarcillin/claulanate


  • Active against Pseudonomas, E.coli, Enterobacter etc and has lower activity against G+
  • Used with aminoglycosides when treating pseudomonal infections
• Carbapenems


  • Imepenem
  • Ertapenem
  • Meropenem
  • Doripenem
• Imepenem


  • Broadest spectrum B-lactam; Neisseria, Haemophilus, Peudomonas, Kelbsella, anaerobes etc
  • More active against G+ (MSSA, Strep) than meropenem and ertapenem
• Ertapenem


  • Good for aerobic G-, poor coverage of Pseudomonas, E. faecalis, Nocardia
• Meropenem


  • Good for aerobic G-
• Doripenem


  • Good for CNS coverage and Pseudomonas
• Monobactams


  Class of antibiotics
• Aztreonam


  • B-lactamase resistant, narrow antibacterial spectrum; aerobic G- rods, H. flu, N. gonorrhoea, E. coli, Pseudomonas
  • Ineffective against G+ and anaerobic organsisms and may cause superinfection with G+ bacteria
• Glycopeptides


  Class of antibiotics
• Vancomycin


  • Not well absorbed orally
  • Inhibits peptidoglycan formation
  • Produced by Streptomyces orientalis
  • Active against most G+ organisms, S. pneumonia, Clostridia, Enterococcus, MRSA (septicaemia and endocarditis) and Staph. Epi
  • Synergy with aminoglycosides
• Polymyxin


  Inhibitor of cytoplasmic membrane
• Polymyxin


  • Binds to membrane of G- and alters permeability (leakage and cell death)
  • Produced by Bacillus polymyxa
  • Decreased G+ coverage
  • Active against Pseudomonas, Serratia, E. coli, Klebsiella and Enterobacter
• Colistin


  Inhibitor of cytoplasmic membrane
• Inhibitors of protein synthesis

  Target bacterial ribosomes (70S), high levels will interact with mammalian ribosomes (80S)
• 30S binders


  • Aminoglycosides
  • Tetracyclins
  • Mupirocin
• Aminoglycosides


  • Bind to 30S and cause it to malfunction, blocking initiation of translation
  • Work against many G- and some G+
  • Non-active against anaerobes
• Tetracyclins


  • Bind 30S to block attachment of tRNA
  • Broad-spectrum
  • Binds to Ca in bone and teeth, can discolour teeth. Should be avoided by children <8
  • Pumped out to prevent accumulation by resistant organisms
• 50S binders


  • Macrolides
  • Clindamycin
  • Chloramphenicol
  • Streptogramins
• Macrolides


  • Bind to 50S to prevent protein synthesis from continuing
  • Effective against G+, used as an alternative to penicillin sensitive patients e.g. Strep, Staph, Pneumococci, Clostridia as well as atypical bacteria e.g. Mycoplasma, Chlamydia, Ledionella
  • Ineffective against meningitis, cannot cross BBB
• Lincosamides


  • Binds 50S subunit
  • Covers Strep, Staph, B. fragile, anaerobes but not Clostridium difficile
  • Avoid Clindamycin as it commonly causes C. difficile