Micro LO 4

  1. Describe the most important mechanism explaining how bacteria become antibiotic resistant. Describe at least one other mechanism of antibiotic resistance.
    • Transferring of plasmids -> bact become resistant to
    • antibiotics. Plasmids passed around are “R-factors” (“r” stands for “resistance”):
    • - enzymes (to break down antibiotic)
    • - pumps (allow bact to pump out antibiotic)
    • Bact also become resistant by:
    • 1) forming biofilms (bact at bottom don’t come into contact w antibodies)
    • 2) mutate (selecting antibiotic-resistant bact)
    • 3) change structure of what antibiotic (abx) is targeting -> may remove cell walls
    • 4) metabolic pathways
  2. State where antibiotics were first isolated from and how semi-synthetic and synthetic agents improve on these antibiotics.
    • abx first isolated from bact. & fungi -> anti (against) and biotic (life). Bact and fungi kill off whatever’s growing in their area. Bact and fungi were original sources.
    • Take “natural” abx -> modify them in the lab -> get “semi-synthetics” (aka: second generation). Want increased range and stability or increasing bacteriocidal abilities.
  3. Define bactericidal, bacteriostatic and bacteriolytic agents. Describe broad spectrum vs. narrow spectrum antibiotics and the advantages and disadvantages of each.
    • bacteriocidal: “killing” the bact.
    • bacteriostatic: stop bact from dividing (gentler on your flora than bacteriocidal; also lets your body see the bact and mount an immune response. CONS: if someone’s immunocompromised, they won’t be able to kill the bact)
    • bacteriolytic: “lyses” bact. à makes them leaky
    • broad spectrum Ab: Gram +/- CONS: Damages pt flora.
    • narrow spectrum Ab: Gram – (like enteric bact after abdominal surgery). If you have myco. TB, you’ll get super narrow spectrum. CONS: if you give wrong abx, you’ve just allowed the real bact to grow one week more.
    • A broad-spectrum antibacterial drug can inhibit a variety of gram-positive and gram-negative
    • bacteria, whereas a narrow-spectrum drug is active only against a limited variety of bacteria.
  4. Describe the MIC test. Is a higher or a lower MIC test desirable? How does this compare with an agar diffusion method? The MBC test?
    • - MIC: Minimal Inhibitory Concentration. Use for Bacteriostatic activity: Level of antimicrobial
    • activity that inhibits the growth of an organism. This is determined in vitro by testing a standardized concentration of organisms against a series of
    • antimicrobial dilutions. The lowest concentration that inhibits the growth of the organism is referred to as the minimum inhibitory concentration (MIC).
    • - MBC: Use for Bactericidal activity: Level of antimicrobial activity that kills the test organism. This is determined in vitro by exposing a standardized concentration of organisms to a series of antimicrobial dilutions. The lowest concentration
    • that kills 99.9% of the population is referred to as the minimum bactericidal concentration (MBC).
    • - Kirby-Bauer test: agar diffusion test. Make a lawn
    • of bact. Buy Ab disks and you “plop” them on -> look for clearing around the disk, called “zone of inhibition”. Get some drug-resistant bact. in zones of inhibition!
  5. List the 9 desirable properties of antibiotics.
    • soluble – can it “get to” infection
    • slowly breaks down/slowly excreted – only have to take this guy once a day, rather than 6 times a day
    • selectively toxic – leaves flora alone
    • pH stable
    • NOT create an allergy
    • Drug resistance RARE
    • Small dose
    • Bacteriocidal vs bacteriostatic preference
    • Active and stable in pus
  6. Define synergistic and antagonistic effects of antibiotics and selective toxicity.
    • synergistic: two things work together and you get more effect than you would from one thing on
    • it’s own… like prescribing two Abs together
    • antagonistic: two drugs cancel each other out
    • dentists should avoid combination therapy
  7. Penicillin V Oral & Penicillin G parenteral
    • Target: cell wall
    • Class: B-lactam
    • MO: Interferes w cross-linking of peptidoglycan
    • Uses: Gram + bact & Gram - cocci
    • * B-lactamase gene on R factors
    • * Staph is resistant!
  8. Methicillin, Cloxacillin, Oxacillin
    • Target: cell wall
    • Class: B-lactam
    • MO: interferes w cross-linking of peptidoglycan
    • Uses: 2nd generation penicillin Staph infxns
    • *B-lactamase resistant (penicillinase-resistant)
    • * Anti-staphylococcal penicillins (but MRSA has emerged)
  9. Ampicillin & amoxicillin
    • Target: cell wall
    • Class: B-lactam
    • MO: interferes w cross-linking of peptidoglycan
    • Uses: 3rd generation penicillin. More effective against Gram - bacilli
    • * "extended spectrum penicillins"; common dental prophylaxis
    • * ampicillin: sulbactam & amoxicillin: clavulanate (augmentin) have B-lactamase inhibitors
  10. Cephalosporin
    • Target: cell wall
    • Class: B-lactam
    • MO: interferes w cross-linking of peptidoglycans
    • Uses: BROAD spectrum. 4th generation (each generation is broader spectrum)
    • * effective against some Gram -; more resistant to B-lactamase
    • * antabuse reaction. 10% of penicillin allergic
  11. Imipenem
    • Target: cell wall
    • Class: B-lactam Carbapenems
    • MO: interferes w cross-linking of peptidoglycan
    • Use: BROAD spectrum
    • * resistant to B-lactamase
    • * given w cilistatin to decrease toxicity
  12. Aztreonam
    • Target: cell wall
    • Class: B-lactam Monobactams
    • MO: interferes w cross linking of peptidoglycans
    • Uses: NARROW spectrum aerobic, Gram -; resistant to B-lactamase
    • * not widely used
    • * given IV, IM, and inhaled
  13. Vancomyocin
    • Target: call wall
    • Class: NON-B-lactam Glycopeptide
    • MO: Cell wall synthesis INHIBITOR
    • Uses: Gram + bacteria; limited effect against Gram -
    • * used for multidrug resistance bact (MRSA) and endocarditis
  14. Bacitracin
    • Target: cell wall
    • Class: topical
    • MO: stops cell wall synthesis
    • Uses: Gram + Staph AND Group A Strep
    • * mostly topical
    • * nephrotoxic if systemic - not well absorbed from GI
  15. Isoniazid
    • Target: cell wall
    • Class: Anti-TB
    • MO: Inhibits mycolic acid synthesis
    • Uses: Mycobacterium tuberculosis
    • *long treatment times needed
  16. Rifampin & Rifabutin
    • Target: RNA synthesis
    • Class: Rifamycins
    • MO: transcription initiation
    • Uses: Mycobacterium TB
    • *Hepatotoxic
  17. Lincomycin, Clindamycin
    • Target: Protein Synthesis
    • Class: Lincosamides
    • MO: Translation inhibitor. Blocks 50 S ribosome; inhibits translocation
    • Uses: Anaerobic Gram + OR Gram - bacteria
    • * pseudo-membranous colitis (from C. diff); common dental proph.
    • * R factor that methylates rRNA and prevents abx binding to ribosomes
  18. Erythromycin, Clarithromycin, Azithromycin
    • Target: protein synthesis
    • Class: macrolides
    • MO: translation inhibitor. Binds 50 S ribosome.
    • Uses: Gram + bact. Other anaerobes not killed at oral admin levels (why you choose penicillins)
    • * GI problems. Ototoxic. Use if penicillin allergies. Effective against B lactamase + organisms
    • * Increases theophylline levels. R factor that methylates rRNA and prevents abx binding to ribosomes
  19. Streptomycin, Gentamicin, Tobramycin
    • Target: protein synthesis
    • Class: Aminoglycosides
    • MO: translation inhibitor. Blocks 30 S ribosome
    • Uses: effective against Gram + and Gram - anaerobes & Gram - rods
    • * requires oxygen for transport into bacteria; not effective against anaerobes
    • * Given IV or IM. Damage 8th cranial nerve. Nephrotoxic
  20. Tetracycline, Doxycycline, Minocycline
    • Targets: Protein synthesis
    • Classs: Tetracyclines
    • MO: translation inhibitor. Blocks 30 S subunit. Stops tRNA binding.
    • Uses: BROAD spectrum: many Gram + and Gram -. Some Rickettsiae, Mycoplasma, and Chlamydia
    • * discolors developing teeth. Photosensitivity. Used as mouthwash for 2ndary infxn w oral ulceration.
    • * antacids, dairy, iron, and zinc reduce absorption. R factor that alters bacterial cell membrane and decreases permeability to abx.
  21. Chloramphenicol
    • Target: protein synthesis
    • Class: Chloramphenicol
    • MO: Blocks 50 S ribosome. Inhibits peptidyl-transferase
    • Uses: Some Gram + cocci, Gram - aerobes, anaerobes, Rickettsia, Chlamydia, Mycoplasma, and salmonella
    • * bone marrow toxicity
    • * limited use - severe Salmonella and B-lactam sensitive patients w bacterial meningitis
  22. Nystatin, Amphotericin
    • Target: cell membrane
    • Class: Polyene
    • MO: binds ergosterol in fungal cell membrane
    • Uses: Candida, Cryptococcus
    • *FUNGAL cell membranes
    • * these are anti-fungals; ergosterol is unique to fungi
  23. Chlorhexidine
    • Target: cell membrane
    • Class: antiseptic mouthwash
    • MO: membrane disruption
    • Uses: both Gram + and Gram - bact; more effective against Gram +
    • * used as a surgical scrub and as a mouthwash. Mouthwash binds to oral tissues has persistent effect.
    • * inactivated by SLS and MFP in toothpaste - don't use together
  24. Polymyxin
    • Target: cell membrane
    • Class: topical
    • MO: detergent action
    • Uses: Gram - (binds LPS in cell wall)
    • *skin, eye infxns
    • * Neurotoxic, nephrotoxic, not GI stable if used internally
  25. Metronidazole
    • Target: DNA synthesis
    • Class: Metronidazole
    • MO: strict anaerobes are sensitive and some protozoa
    • Uses: anaerobes EXCEPT Actinomyces
    • *often used to treat pseudo-membranous colitis
    • *antabuse effect w alcohol
  26. Ciprofloxacin
    • Target: DNA synthesis
    • Class: quinolones, Fluoroquinolones
    • MO: inhibit DNA gyrase-transcription inhibitor
    • Uses: Gram - rods, Neisseria some Gram +; not anaerobes
    • *can damage cartilage and growing bone
    • * not used in kids or in pregnancy
  27. Sulfadiazine, Trimethoprim
    • Target: metabolism
    • Class: Sulfonamides
    • MO: blocks folic acid synthesis -> need folate for DNA
    • Uses: Gram + and Gram - Actinomyces, Nocardia, and Chlamydia
    • *cause hemolytic anemia in patients w G6PD deficiency
    • * allergy causer, renal toxicity. Trimethoprim: good for UTI b/c it's excreted in urine
Card Set
Micro LO 4
Micro- Antibiotics lecture - Rabe