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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
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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.
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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.
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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!
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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
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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
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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!
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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)
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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
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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
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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
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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
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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
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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
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Isoniazid
- Target: cell wall
- Class: Anti-TB
- MO: Inhibits mycolic acid synthesis
- Uses: Mycobacterium tuberculosis
- *long treatment times needed
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Rifampin & Rifabutin
- Target: RNA synthesis
- Class: Rifamycins
- MO: transcription initiation
- Uses: Mycobacterium TB
- *Hepatotoxic
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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
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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
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