TREATMENT OF BACTERIAL DISEASES

• Antimicrobial agent


  Any substance of natural, semi-synthetic or synthetic origin that kills microbes (bacteria, fungi, virus) or prevents their multiplication/growth, reducing their pathogenic effect
• Types of antimicrobial agents

  • Natural (e.g. streptomycin, penicillin, tetracycline)
  • Semi-synthetic (e.g. ampicillin, amikacin)
  • Synthetic (e.g. sulfonamide, enrofloxacin, marbofloxacin)
• Broad-spectrum antibiotics


  Active against both Gram(+) and Gram(-) microorganisms
• Narrow-spectrum antibiotics


  Limited activity and primarily only useful against particular species of microorganisms
• Bactericidal agents


  Kill bacteria and reduce the total number of viable organisms
• Bacteriostatic agents


  Inhibit growth and replication of bacteria, thus allowing the host immune system to complete pathogen elimination
• Discovery of Penicillin (fungus Penicillium notatum) by Alexander Fleming


  1928
• Mode of action of antibacterial agents

  Interfere with bacterial cell growth by interacting with a vital structure or blocking a metabolic pathway and preferably exhibit selective toxicity (i.e., without direct toxicity for hosts receiving treatment)
• Cell wall synthesis inhibitors

  • β-lactam antibiotics (e.g. penicillin, ampicillin, cephalosporin, carbapenem, monobactam) inhibit peptidoglycan synthesis by binding to penicillin binding proteins (PBP) and promote autolysin activity causing cell lysis
  • Glycopeptides (e.g. vancomycin, teicoplanin) inhibit peptidoglycan synthesis by binding to amino acids (d-alanyl-d-alanine) in the cell wall, preventing the addition of new units
• Protein synthesis inhibitors


  • Aminoglycosides (e.g. gentamicin, amikacin) inhibit 30S subunit of bacterial ribosome
  • Tetracyclines (e.g. oxytetracycline, chlortetracycline) inhibit 30S subunit of bacterial ribosome
  • Macrolides (e.g. erythromycin, azithromycin) inhibit 50S subunit of bacterial ribosome
  • Chloramphenicol inhibits 50S subunit of bacterial ribosome
  • Lincosamides (e.g. clindamycin) inhibit 50S subunit of bacterial ribosome
• DNA synthesis inhibitors


  • Quinolones (e.g. nalidixic acid, enrofloxacin) inhibit enzymes which separate DNA strands (e.g. DNA gyrase)
  • Metronidazole causes breaks in DNA strands and is particularly effective against obligate anaerobic bacteria (e.g. Clostridium)
  • Rifampin inhibits RNA polymerase during transcription, active against Mycobacterium tuberculosis
  • Mupirocin inhibits tRNA synthetase during translation
• Folic acid synthesis inhibitors

  • Sulphonamides interfere with formation of folic acid, essential precursor for nucleic acid synthesis. Inhibitors of p-aminobenzoic acid (PABA) in the folic acid metabolism cycle.
  • Trimethoprim interferes with formation of folic acid, essential precursor for nucleic acid synthesis. Blocks the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid
• Antimicrobial susceptibility testing (AST)

  1. An in vitro test (performed outside an animal) of the sensitivity of bacteria to one or more antibiotics

  2. Three main methods: Disk diffusion test, concentration gradient diffusion test, and broth dilution test
• Disk diffusion test ("Kirby Bauer")

  1. Based on the diffusion of an antibiotic on solid cultures

  2. Must use a bacterial isolate in pure culture

  3. Standardized bacterial inoculum spread on agar plate

  4. Standardized antibiotic disks placed on the plate and incubated. The antibiotic diffuses in the agar and the concentration declines as it distances from the disk.
• Minimum inhibitory concentration (MIC)


  Highest dilution of an antibacterial agent that inhibits growth of an isolate in the broth (naked eye)
• Minimal bactericidal concentration (MBC)


  Highest dilution of a drug that can kill a particular bacterium (demonstrated by subcultures)
• Concentration gradient diffusion test

  1. Method that uses both principles from diffusion and dilution

  2. MIC values are obtained at the point of intersection between the strip and the ellipse of the zone of inhibition
• Antimicrobial susceptibility testing (AST)


  Leads to therapy success or failure
• Antimicrobial resistance is a global threat
• Antimicrobial resistance generation


  1. Innate resistance: preexisting genomic property (mutation or gene)

  2. Acquired resistance: acquired by mutation or horizontal gene transfer (conjugation, transduction and transformation)
• Antimicrobial resistance mechanisms
• Providers should not overprescribe for mild and non-bacterial infections or overselect broad spectrum, costly or last resort drugs
• Patients/clients should not engage in non-compliance or self-medication
• Industry should not engage in misleading promotion or competition