Chapter 12

• Ideal chemotherapeutic agent

  • Selectively toxic to microbe but non-toxic to the host
  • Microbicidal rather than microbystatic
  • Relatively soluble; functions even when highly diluted in body fluids
  • Remains potent long enough to act, and is not broken down or excreted prematurely
  • Doesn't lead to the development of antimicrobial resistance
  • Complements or assist the activities of the host defenses
  • Remains active in tissues and body fluids
  • Readily delivered to the sight of infection
  • Reasonably priced
  • Does not disrupt the host's health by causing allergies or predisposing the host to other infections
• Reasons drugs fail to be approved for human use

  • Not selectively toxic
  • Cannot reach target tissues
  • Are resistant already
  • Mixed infections
  • Destroy the gut
  • Are expensive and not easy to administer
• Difficulty of making antiviral and antifungal meds

  • Viruses need host cells in order to function and reproduce so it is difficult to make antivirals that will not harm the host cell
  • It is hard to make effective antifungals because humans and funguses are eukaryotes so they do not have many differences
• Broad spectrum


  Antimicrobials that are effective against a wide variety of microbial types, for example, a drug effective against both gram-positive and gram-negative bacteria
• Narrow spectrum


  Microbials that are effective against a limited array of microbial types, for example, a drug effective mainly on gram-positive bacteria
• Prophylaxis


  Use of drugs to prevent imminent infection of a person at risk
• Antimicrobial Chemotherapy


  The use of drugs to control infection
• Antimicrobials

  An all-inclusive term for any antimicrobial drug, regardless of what type of microorganism it targets
• Antibiotics

  Substances produced by the natural metabolic processes of some microorganisms or created by scientists, they can inhibit or destroy microorganisms and generally, the term is used for drugs targeting bacteria and not other types of microbes
• Semi synthetic drugs

  Drugs that are chemically modified in the laboratory after being isolated from natural sources
• Synthetic drugs


  Drugs that are produced entirely by chemical reactions within a laboratory setting
• Therapeutic index


  Range of doses of a medication where it will not cause adverse effects. The higher the index the better
• Toxic dose

  Minimum dose that causes toxicity
• Minimal inhibitory concentration

  Smallest concentration to prevent microbial growth
• Therapeutic index


  Calculated by Toxic dose/Minimal inhibitory concentration
• MIC matters in a clinical setting
• Kirby Bauer


  You lay antibiotic soaked disks onto a bacterial lawn, after incubation observe size of zone of inhibition to determine if the bacteria is resistant, susceptible or intermediate
• etest

  You place antibiotic soaked strips onto a bacterial lawn, after incubation look at the numbers on the strip which will tell you the minimum inhibitory concentration
• Broth MIC assays

  Where you use serial dilutions to determine the MIC
• Five targets of inhibition

  • Cell wall synthesis
  • Inhibition of nucleic acid structure and function
  • Inhibition of protein synthesis (especially ribosomes)
  • Interfere with cell membrane structure or function
  • Inhibition of folic acid synthesis
• Inhibiting cell wall synthesis

  • Will not affect human cells because only bacteria have peptidoglycan cell walls
  • Inhibition of the nucleic acid structure is selectively toxic because it inhibits gyrase and RNA polymerase which are very different than humans
• Inhibition of proteins

  • Done by antibiotics binding to receptors that are exclusively only in bacterial ribosomes
• Inference of cell membrane

  • Structure and function is selectively toxic because it disrupts selective permeability in gram-negative bacteria
• Inhibition of folic acid

  • Selectively toxic kind of because it has competitive inhibition
  • PABA which is a substrate for folic synthesis is blocked by sulfa antibiotics
  • Folic acid is used in bacteria to create DNA
• Value of bacteriostatic drugs

  There is a lower chance of toxic shock and there are more tolerable side effects compared to killing cells
• Toxicity of inhibition targets

  • Least toxic: Inhibition of folic acid
  • Most toxic: Cell wall because humans do not have a cell wall
• Mutations and HGT


  Result in bacteria becoming resistant to an antibiotic, if they continue to occur the number of antibiotics the bacteria will be resistant to
• Antibiotic resistance increase

  • It develops from mutations and horizontal transfers occurring
  • The use of antibiotics increases as the number of antibiotic resistance increases
  • Resistance can be spread through poor hygiene practices, contact and by eating meat
  • In agriculture they use antibiotics to increase the size of the animal, these antibiotics are being transferred to humans
• 5 mechanisms of antibiotic resistance

  • Enzyme inactivation and modification
  • Modification of the antibiotics target site
  • Overproduction of the target
  • Replacement of the target site
  • Efflux and reduced permeability
• Humans and agriculture

  Humans ingest the antibiotics that is in the water and food from agriculture, this gives the same bacterial infections and antibiotic resistance
• Ways to fight antibiotic resistance

  • Vaccines
  • Phage Therapy
  • Hygiene
  • H2O quality
  • Immunotherapy
  • Antibiotics
  • Money
• It takes 23 years to create a new antibiotic
• Problems with C.diff

  There is a dwindling number of antibiotics that can treat C. diff, the problem is that C. diff occurs as a result of the gut microbiota being very diminished
• Fecal implants


  Worked in being able to increase the gut microbiota so that it can fight C. diff