Antimicrobial Drugs

  1. Compare and contrast the following terms: antibiotic/antimicrobial drug, antibiotic/semisynthetic/synthetic drugs, bactericidal/bacteriostatic drugs, broad spectrum/narrow spectrum drug.

    1. Antibiotic: low molecular weight substance produced by a microorganism that inhibits or kills other microorganisms at low concentrations. (Could be antibacterial, antifungal, antiprotozoal, etc.)

    2. Antimicrobial drug: can be natural or synthetic. It inhibits or kills other microorganisms without causing damage to the host. 

      1. Inhibit processes that are unique to bacteria. 

    3. Semisynthetic drug: natural antibiotics might be altered in the lab to produce variants with more desirable activities 

    4. Synthetic drug: 

    5. Bactericidal: kill bacteria

    6. Bacteriostatic: inhibit growth of microbes, but does not kill them; relies on host immune system to get rid of the bacteria

    7. Broad spectrum: inhibit or kill most bacteria (may cause unnecessary damage to the microbiome). 

    8. Narrow spectrum: inhibit or kill a certain number of bacteria 

  2. Who discovered arsphenamine (Salvarasan)? What was it used for?

    1. Paul Erlich—would stain microbial pathogens, making it easier to target and kill them, but not stain human cells. 

      1. Syphillus 

  3. Who discovered sulfa drugs? What type of drugs are these?

    1. Gerhard Domagk—special red dye that treats Steptococcus

    2. Synthetic

  4. Who discovered penicillin? Why did it take so long to bring this drug into general use? Who won the Nobel Prize?

    1. Alexander Fleming—hard to extract enough penicillin from mold strains

      1. Observed portions of no growth (allowing certain bacteria to have a competitive advantage)

      2. Not enough penicillin was produced from the original strain—search for super-strains

  5. Who discovered streptomycin? Where did this drug come from?

    1. Selman Waksman—soil bacteria can produce a wide variety of antibiotics (soil bacteria=Streptomyces)

  6. In what decade were the greatest number of antibiotics discovered? Why are so few being discovered now?

    1. 1960s

    2. Few now because the most common antibiotics have already been found, and research is very expensive. 

  7. Outline at least 4 different targets of antibacterial drugs. Why is each selectively toxic? Give an example of each one.

    1. Protein synthesis: selectively toxic because prokaryotic and eukaryotic ribosomes are composed of different rRNAs and proteins. 

    2. RNA polymerase: rifampin

    3. Cell membrane disruptors:

    4. Nucleic acid synthesis: fluoroquinolones (unwinding), rifampin, sulfa drugs, trimethoprim

    5. Cell wall synthesis: Penicillins, cephalosporins, etc.

    6. Folate synthesis: 

  8. Why are bacteria sensitive to sulfa drugs are we are not?

    1. We don’t follow the same metabolic pathways that synthesize folic acid as bacteria. 

  9. What do b-lactam drugs have in common? Why do b-lactam drugs target bacteria that are actively dividing?

    1. Penicillins, cephalosporins, etc.

    2. Ring of 3 Cs and 1 N

    3. Only work on actively-dividing cells

    4. Inhibit cell wall synthesis 

      1. Prevent peptidoglycan cross-linking

  10. Discuss several considerations that must be taken into account when prescribing an antibiotic.

    1. Where does it go in the body?

    2. Many drugs cannot cross blood-brain barrier

    3. Half-life

    4. Microbiome can influence drug metabolism

    5. Is the patient immunocompetent (if so, you can use a bacteriostatic drug)

    6. Is the patient drug resistant?

  11. Compare and contrast three basic types of antimicrobial drug resistance.

    1. Intrinsic: structure of the microbe prevents drug action

      1. Penicillin on mycoplasma bacteria or Gram-negative bacteria

    2. Chronic resistance: Persisters/altered physiological state/biofilms: cells aren’t actively dividing

      1. May continue growing even after patient has finished the drug

    3. Acquired resistance: genetic change that leads to resistance

  12. Why are bacteria in biofilms more resistant to antimicrobial drugs?

    1. Contain persister cells

    2. Difficult to diffuse into the slimy EPS matrix

    3. ECF proteins that can combine or sequester drugs so they cannot reach their target 

    4. Contain enzymes that can deactivate drugs