Antibiotics I Flashcards

1
Q

minimal inhibitory concentration (MIC)

A

concentration of antimicrobial that inhibits growth of an organism

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2
Q

minimal bacteriocidal concentration (MBC)

A

concentration that KILLS bacteria

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3
Q

breakpoint

A

the MIC that is used to designate between sensitive and resistant; arbitrarily set by a committee

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4
Q

if MIC > breakpoint, the organism is (resistant or sensitive?)

A

RESISTANT

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5
Q

if MIC < breakpoint, the organism is (resistant or sensitive?)

A

SENSTITIVE (susceptible)

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6
Q

pharmacodynamics for beta lactams

A

time above MIC
*needs to be > 50%
*continuous infusion is good for this

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7
Q

pharmacodynamics for aminoglycosides

A

Cmax/MIC
*needs to be > 5
*high dosage once a day is good for this (gets the highest peak possible)

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8
Q

pharmacodynamics for fluoroquinolones

A

area under the curve (AUC) / MIC
*needs to be > 35

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9
Q

synergy

A

2 antibiotics work better together than either one of them could do alone
*ex. one inhibits cell wall and one inhibits ribosome

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10
Q

antagonism

A

two antibiotics “get in each other’s way”
*usually when the 2 antibiotics are competing for the same target

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11
Q

which antibiotic classes target cell wall synthesis

A

beta lactams, cephalosporins, carbapenems, vancomycin, bacitran

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12
Q

subclasses of beta lactam antibiotics

A

penicillins, cephalosporins, carbapenems, monobactam (aztreonam)

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13
Q

beta lactam antibiotics - target

A

*binds to penicillin binding proteins (PBPs) in cell wall

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14
Q

beta lactam antibiotics - overview

A

*binds to PBPs in cell wall
*bactericidal
*spectrum dependent on subclasses
*generally good serum, urine, and tissue levels; CSF level variable
*time dependent pharmacodynamics (time above MIC > 50%)

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15
Q

beta lactam ring - structure

A

amide bond - essential for the function of these antibiotics

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16
Q

beta lactam antibiotics - mechanism of action

A

*act on penicillin binding proteins (PBPs; aka transpeptidases) to INHIBIT CROSS-LINKING of PEPTIDOGLYCAN via pentaglycine bridge
*causes osmotic dysregulation, which causes lysis

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17
Q

beta lactam antibiotics - mechanisms of resistance

A
  1. production of beta-lactamases (cleave the beta lactam ring)
  2. alteration of PBPs (so the antibiotic cannot bind)
  3. decreased permeability
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18
Q

how do beta lactamases work in gram positive organisms

A

beta-lactamase diffuses away, leading to weak concentrations of the enzyme
*happens b/c there is only one cell membrane/wall

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19
Q

how do beta lactamases work in gram negative organisms

A

beta-lactamase gets concentrated between the membranes
*leads to more potent activity of beta-lactamases

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20
Q

beta-lactamase inhibitors

A

*bind to beta-lactamase irreversibly at the active site
*often given simultaneously with a beta lactam antibiotic, which “neutralizes” the beta-lactamases

21
Q

what are the 4 beta lactamase inhibitors

A

-clavulanic acid
-sulbactam
-tazobactam
-avibactam

22
Q

penicillin class antibiotics

A
  1. penicillin
  2. aminopenicillins
  3. antistaphylococcal penicillin
  4. extended spectrum (antipseudomonal penicillin)
23
Q

2 important aminopenicillins

A

*ampicillin (IV)
*amoxicillin (PO)
note - augmentin = amoxicillin/clavulanate

24
Q

3 important antistaphylococcal penicillins

A

-methicillin (IV)
-dicloxacillin (PO)
-nafcillin

25
Q

important extended spectrum (antipseudomonal) penicillin

A

piperacillin

26
Q

penicillin G

A

*“prototype” of penicillin
*used for strep, enterococci, and spirochetes
*resistance is NOT a concern in group A and group B strep
*resistance occurs (through altered PBPs) for pneumococcus, enterococci, and viridans strep

27
Q

benzathine penicillin

A

*used for direct observed therapy for syphilis
*has a LONG half-life, so one injection lasts for about 3 weeks

28
Q

resistance mechanism for staph aureus (MRSA)

A

*resistance through altered PBPs
*resistance transferred via MecA operon
*causes resistance to ALL beta-lactams

29
Q

benefit of anti-staphylococcal penicillins

A

bactericidal to staph
(NOTE - developing resistance [MRSA] via altered PBPs)

30
Q

benefit to aminopenicillins

A

*extend the spectrum to include more gram negative rods
*good drug for head/neck and respiratory tract infections

31
Q

benefits to antipseudomonal penicillins (piperacillin)

A

extends activity to include pseudomonas & gram negative rods
*downside: must be given IV

32
Q

type 1 beta lactam allergy (immediate hypersensitivity)

A

*IgE/mast cell mediated
*urticaria (hives) and anaphylaxis
*most serious

33
Q

type 2 beta lactam allergy (innocent bystander)

A

*adherence of drug as a hapten to a cell (attaches to RBC membrane and IgG attacks, lysing the cell)
*hemolytic anemia

34
Q

type 3 beta lactam allergy (“Arthus” immune complex)

A

*serum sickness: fever, glomerulonephritis, arthritis, adenopathy (not all at the same time)
*the penicillin clumps into a ball and antibodies attach; the complex gets stuck in joints, kidneys, etc

35
Q

type 4 beta lactam allergy (delayed hypersensitivity)

A

*most common beta lactam allergy
*T cell mediated
*usually after 7-10 days of antibiotic
*rash, usually with fever
*eosinophilia

36
Q

cephalosporins

A

*subclass of beta lactam antibiotics (bind to PBPs)
*more stable to beta lactamases than other subclasses

37
Q

benefits of cephalosporins

A

*SAFE (high therapeutic to toxicity ratio)
*3rd generation cephalosporin (ceftriaxone) has good CNS penetration

38
Q

1st generation cephalosporins

A

*active against gram positive organisms (Staph and Strep)
1. cefazolin** (IV)
2. cephalothin (IV and PO)

39
Q

2nd generation cephalosporins

A

*active against gram positive and some gram negative organisms (Haemophilus, enterobacteriaceae)
1. cefoxitin (IV)
2. cefuroxime (IV and PO)

40
Q

3rd generation cephalosporins

A

*broader spectrum
1. ceftriaxone (broad spectrum but not pseudomonas; CROSSES BLOOD-BRAIN BARRIER)
2. ceftazadime (good against pseudomonas and other GNRS; loses potency against gram positives)

41
Q

ceftriaxone

A

*3rd generation cephalosporin
*crosses the blood-brain barrier (for bacterial meningitis)
*not effective against pseudomonas

42
Q

4th generation cephalosporins

A
  1. cefepime (broad, GP, GN, includes pseudomonas)
43
Q

5th generation cephalosporins

A

*enhanced antipseudomonal activity
1. ceftolozane (given with tazobactam)

44
Q

MRSA active cephalosporin

A

ceftaroline

45
Q

cefiderocol (new cephalosporin)

A

*uses the bacterial active iron transport channels to penetrate in the periplasmic space of gram negative bacteria
*overcomes many resistance mechanisms because it can cross the outer membrane, even if there is a loss of porins

46
Q

aztreonam

A

*monobactam (beta lactam)
*active ONLY against gram negative AEROBES
*no cross reaction with type 1 hypersensitivity

47
Q

carbapenems

A

*subclass of beta lactams (bind to PBPs)
*one of the broadest spectrums of antibiotics
*can NOT kill MRSA, enterococci, listeria

48
Q

carbapenems - mechanism of resistance

A

*reduced permeability of gram negative rod outer membrane (loss of porins [D2 porin] - antibiotic can’t get in)
*carbapenemases increasing in incidence

49
Q

3 examples of carbapenems

A
  1. imipenem
  2. meropenem
  3. ertapenem