ANTIMICROBIALS

• Antimicrobials (Antibiotics)


  Chemical substances produced by a microorganism with the capacity to inhibit other microorganisms
• Narrow spectrum antimicrobials


  • Effective against a limited number of pathogens
• Narrow spectrum antimicrobials


  • Bacitracin, clindamycin, dapsone, erythromycin, gentamicin, isoniazid, polymyxin B and vancomycin
• Broad spectrum antimicrobials


  • Destroy different kinds of organism
• Broad spectrum antimicrobials


  • Ampicillin, cephalosporin, chloramphenicol, ciprofloxacin, rifampicin, sulfonamines, trimethoprim and tetracycline
• Classification of antimicrobials


  • Natural drugs
  • Semisynthetic drugs
  • Synthetic drugs
• Semisynthetic antimicrobial drugs


  • Ampicillin
  • carbenicillin
  • methicillin
• Bacteriostatic antimicrobial agents


  • Chloramphenicol
  • Dapsone
  • Erythromycin
  • Clindamycin
  • Isoniazid
  • Rifampicin
  • Sulphonamides
  • tetracyclines
• Bactericidal antimicrobial agents


  • Aminoglycosides: gentamicin, amikacin and streptomycin
  • beta-lactams: ceftriazone, imepenem, penicillin and cefotaxime
  • glycopeptides: vancomycin
  • isoniazid
  • quinolones
  • bacitracin
  • metronidazole
• Minimal Inhibitory Concentration (MIC)


  The lowest concentration of a drug that inhibits bacterial growth
• Minimal Lethal Concentration (MLC)


  The lowest concentration of drug that kills bacterial growth
• Therapeutic Index


  The ratio of the toxic dose to the therapeutic dose; the higher the therapeutic index, the more effective the chemotherapeutic agent
• Qualities of a good antimicrobial agent

  • Kill or inhibit pathogens
  • Selective toxicity (cause NO damage to the host)
  • Non allergenic
  • Stable
  • Remain in specific tissues of the body
  • Kill pathogens before they mutate / resistant
• Actions of antimicrobials


  • Inhibiting cell wall synthesis
  • Inhibiting CHON synthesis
  • Inhibiting N.A synthesis
  • Destroying the cell membrane
  • Inhibiting essential metabolites
• Cell wall inhibitor antimicrobials

  • Bacitracin
  • Cephalosporin
  • ampicillin
  • Imipenem
  • Penicillin
  • Cloxacilin, dicloxacillin, mehcillin, nafcillin, oxacillin
  • Amoxicillin, ampicillin, piperacillin, carbenicillin, ticarcillin
  • Vancomycin
  • Isoniazid-acts only on growing cells
  • Carbenicillin
  • Methicillin
• Cell wall inhibitor antimicrobials

  • Cell growths stops and death often follows
  • Most selective antibiotics with high therapeutic index
  • Inhibits transpeptidation enzymes
• Penicillin


  Resembles D-alanyl-D-alanine of the peptidoglycan subunits
• Penicillin types


  • Pen Gin (activated by stomach acids, parenterally)
  • Penicillin V (acid resistant, orally)
  • Penicillinase resistant penicillin- methicillin, nafcillin, oxacillin
• Cephalosporins


  • cephalotin, cefoxitin, ceftriazone, cephalexine, cefixime and cefoperazone
• Ampicillin


  Acid stable, effective for G+, G-
• Vancomycin

  Cup-shaped molecule drug; teicoplanin drug
• Carbenicillin

  Acid stable, Pseudomonas and Proteus
• Inhibitors of protein synthesis

  • 30'S Ribosomes Inhibitors: Tetracycline (bacteriostatic), Aminoglycosides - Streptomycin, Kanamycin, Amikacin, Gentamicin, Tobramycin, Neomycin/Netilmicin, Fusidic acid
  • 50's Ribosomes Inhibitors: Chloramphenicol (bacteriostatic), Macrolides - Erythromycin (bacteriostatic or cidal), Clindamycin (bacteriostatic or cidal), lincomycin
• Inhibition of protein synthesis by 30S ribosomes inhibitors

  Binds with 30s subunit resulting to misreading of mRNA and interferes with aminoacyl-tRNA binding
• Inhibition of protein synthesis by 50S ribosomes inhibitors

  Binds with 50s subunit resulting to inhibition of peptidyl transferase and inhibits peptide chain elongation
• High dosage of tetracycline may lead to live and kidney damage and yellowing the teeth of children
• Chloramphenicol may cause temporary or permanent depression of bone marrow leading to aplastic anemia and leukemia (toxic side effect)
• Aminoglycosides

  • Gentamicin, kanamycin, neomycin, streptomycin and tobramycin, they have cyclohexane ring and may cause deafness and loss of balance (toxic)
• Macrolide antibiotics


  • Erythromycin, clindamycin and azithromycin
• Chloramphenicol and erythromycin bind to 23s rRNA on the 50s ribosomal unit
• Inhibitors of nucleic acid synthesis

  • Rifampin
  • Mitomycin
  • Metronidazole - disruption if DNA, for anaerobic
  • Novobiocin
  • Nitrofurantoin
  • Quinolones and Fluroquinolones - Ciprofloxacin, Nalidixic Acid, Norfloxacin, Levoflaxin: interfere with the DNA gyrase and replication-Highly effective for enteric bacteria E.coli
• Inhibitors of enzyme activity/metabolites

  • Folic acid inhibitors: Sulfonamides, Trimethoprim, SXT (trimethoprim-sulfamethoxazole), Dapsone
  • Anti-TB drugs: S-I-R-E, Inhibits synthesis of Cord factor (mycolic acid)
• Cell membrane disruptors


  • Polymixin B (g- bacteria Pseudomonas)
  • Polymixin E (Colistin)-ointment
  • Polyenes (amphoteracin B)
  • Azole (Clotrimazole, Ketoconazole, Fluconazole)
• Types of drug resistance

  • Intrinsic resistance: Lack specific target site (mycoplasma), Unable to reach its site of action (ribosome)
  • Extrinsic resistance: Cannot bind to bacterial cell (mutation), Cannot pass through the cell membrane (mutation- cell membrane permeability), Destroyed by the enzyme (beta lactamase) - Penicillinases and Cephalosporinase, Pump out of the cell before it can damage or kill cell (MDR pump)
• Strategies to overcome beta-lactam resistance

  • Beta lactam inhibitor with beta lactam antibiotic: Clavulanic acid with amoxicillin (Augmentin), Sulbactam with ampicillin (Unasyn)