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Clinical Microbiology > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Differential toxicity

A

Based on the concept that the drug is more toxic to the infecting organism than to the host

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2
Q

Minimum inhibitory concentration (MIC)

A

Minimum concentration of antibiotic required to INHIBIT the growth of the test organism

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3
Q

Minimum bactericidal concentration

A

Minimum concentration of antibiotic required to KILL the test organism
(allows less than 0.1% of the original inoculum to survive)

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4
Q

Prophylaxis

A

Antimicrobial agents are administered to prevent infection

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5
Q

Treatment

A

Antimicrobial agents are administered to cure existing or suspected infection

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6
Q

Therapeutic index

A

Toxic dose/ Effective dose
Drugs with a low TI may require therapeutic drug monitoring to ensure drug levels are both adequate for maximal efficacy, but not toxic to the patient

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7
Q

2 classes of drugs that have a small TI

A

Aminoglycosides

Vancomycin

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8
Q

What is the ideal antibiotic

A

No/low toxicity to the host (well tolerated)
Low propensity for development of resistance
Does not induce hyper-sensitivities in the host
Rapid and extensive tissue distribution
Relatively long half-life (10-12 hours)
Free of interactions with other drugs
Convenient for administration
Relatively cheap

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9
Q

4 advantages to combination therapy

A
  1. Treating polymicrobial infections
  2. Initial empiric therapy (broad coverage)
  3. Synergy
  4. May prevent the emergence of resistance (TB, S aureus, H pylori)
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10
Q

4 disadvantages of combination therapy

A
  1. Antagonism
  2. Cost
  3. Increased risk of side effects/drug drug interactions
  4. Usually not necessary for maximal efficacy
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11
Q
  1. Transformation
  2. Conjugation
  3. Transduction
A
  1. Transfer of free DNA
  2. Plasmid transfer
  3. Transfer by viral delivery
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12
Q

How long should you avoid repeating macrolide prescriptions to minimize resistance?

A

3 months

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13
Q

6 general mechanisms of resistance

A
  1. Altered permeability
  2. Inactivation/destruction of antibiotic
  3. Altered binding site
  4. Novel binding sites
  5. Efflux mechanisms
  6. Bypass of metabolic pathways
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14
Q

3 main classes of cell wall synthesis inhibitors

A

Beta lactams (penicillins, cephalosporins, carbapenems)
Glycopeptides (vancomycin)
Fosfomycin

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15
Q

2 examples of penicillins

A

Cloxacillin (anti-staphylococcal)

Piperacillin (anti-pseudomonal)

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16
Q

What changes as you move from first to fifth generation cephalosporins?

A

First is really good against gram positives

As you move up you lose gram positive and gain gram negative activity

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17
Q

Beta lactam drugs are substrate analogs of what?

A

D ala D ala

Competitive inhibitors of PBPs

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18
Q

Penicillin binding proteins

A

Essential enzymes involved in bacterial cell wall production
Transpeptidases
Target of beta lactam antibiotics

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19
Q

4 mechanisms of beta lactam resistance

A
  1. Production of a beta lactamase (most common)
  2. Altered PBP
  3. Novel PBP
  4. Altered permeability
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20
Q

What is the most common beta lactam/beta lactamase inhibitor combo?

A

Amoxicillin-clavulanic acid

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21
Q

2 examples of beta lactamase inhibitors

A

Clavulanic acid

Tazobactam

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22
Q

Glycopeptides

A

Vancomycin
Gram positives only!
Bind to the terminal D ala of nascent cell wall peptides and prevent cross linking of these peptides to form mature peptidoglycan
Sterically hinders its addition onto cell wall

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23
Q

Vancomyin resistance

how, effects, which 2 organisms

A

Bacteria substitudes D-lac for D-ala
Vancomycin cannot bind and you get normal cell wall synthesis
Enterococcus/ S aureus is main problem

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24
Q

Fosfomycin

A

Inactives the enzyme enol-pyruvyl transferase
Blocks condensation of UDP-N-acetylglucosamine with p-enolpyruvate
Works in the cytoplasm to inactivate the enzyme

25
Q

Fluoroquinolones

A

Really good to use against atypical pathogens
Concentration dependent and highly bactericidal
Moxifloxacin is the best
Good against gram positives and gram negatives
DNA synthesis inhibitors

26
Q

Two enzymes fluoroquinolones target

A

DNA gyrase
Topoisomerase 4
Inhibit DNA synthesis

27
Q

Qnr

A

Binds to protein and protects DNA gyrase from binding of the antibiotic

28
Q

Main adverse effect of fluoroquinolones

A

Cartilage toxicity/ tendon rupture

Restrict pediatric usage

29
Q

Metronidazole

A

Go to anaerobic drug

Works by damaging DNA - inhibits nucleic acid synthesis

30
Q

3 benefits of metronidazole

A

Bioavailable - can take orally
Very little resistance
Cheap

31
Q

4 main classes of drugs that inhibit protein synthesis

A
  1. MLS (macrolides, lincosamides, streptogramins)
  2. Tetracyclines
  3. Aminoglycosides
  4. Linezolid
32
Q

3 drugs in the macrolide class

A

Erythromycin
Clarithromycin
Azithromycin

33
Q

Macrolides

A

Bind to 50S subunit of bacterial ribosomes to inhibit protein synthesis
Works by:
1. Blocking growth of nascent peptide chain by stimulating dissociation of the peptidyl-tRNA from the ribosome
2. Inhibiting assembly of new large ribosomal subunits
Good against atypical pathogens

34
Q

2 mechanisms of macrolide resistance

A 
Efflux pump (M phenotype)
Target site modification erm (MLS phenotype)
35
Q

Clindamycin

A

Anaerobic
Gram positives
Doesn’t work well against gram negatives
Associated with C difficile colitis

36
Q

Tetracyclines

A

Tetracycline, Doxycycline, Minocycline
Bind reversibly to the 30S ribosomal subunit
Really good against atypical
Discolouration of teeth

37
Q

Aminoglycosides

A

Gentamicin, tobramicin, amikacin
Highly bactericidal
Bind to irreversibly to 30S subunit of ribosomes and inhibit protein synthesis
Cannot use these to treat anaerobic infections or abscesses

38
Q

Why cant you use aminoglycosides to treat anaerobic infections or abscesses?

A

They have to be actively transported into the bacterial cell – requires oxygen for transport

39
Q

What is the most common form of resistance for aminoglycosides?

A

Enzymatic modification

40
Q

2 adverse effects of aminoglycosides

A

Ototoxic

Nephrotoxic

41
Q

Colistin

A

Gram negative agent with some gram positive activity
Also called polymyxin
Relatively toxic
Disrupts outer membrane

42
Q

Daptomycin

A

Gram positive agent
You cannot use this drug to treat respiratory tract infections because surfactant inactivates it
Works just as well as vancomycin and has a larger TW, but is still under patent so really expensive
Inserts into membrane and causes depolarization and potassium flux

43
Q

The beta-haemolytic strep are NEVER resistant to…

A

Penicillin or any beta lactam

44
Q

Enterococcus are all intrinsically resistant to what class of drugs?

A

Cephalosporins

ALWAYS

45
Q

E. cloacae and Citrobacter can have inducible resistance to what type of drugs?

A

Beta lactams

46
Q

Nitrocephin disks

A

Quick screen for beta-lactamase production
Nitrocephin is a cephalosporin
When you break open the beta lactam ring it changes color

47
Q

The Kirby-Bauer Test

A

Disc diffusion method
Antibiotic impregnated filter disc
Susceptibility test against more than one antibiotic measuring size of inhibition zone
The qualitative results of filter disk diffusion assay correlated well with quantitative results from MIC tests

48
Q

Factors Affecting Size of Zone of Inhibition:

  1. Inoculum density
  2. Timing of disc application
  3. Temperature of incubation
  4. Incubation time
A
  1. Larger zones with light inoculum and vice versa
  2. If after application of disc the plate is kept for longer time at room temperature, small zones may form
  3. Larger zones are seen with temps less than 35degC
  4. Ideal 16-20 hours - less time does not give reliable results
49
Q

Factors Affecting Size of Zone of Inhibition:

  1. Depth of the agar medium
  2. Proper spacing of the discs
  3. Potency of antibiotic discs
A
  1. Thin media yields excessively large inhibition zones and vice versa
  2. Avoids overlapping of zones
  3. Deterioration in contents leads to reduced size
50
Q

Factors Affecting Size of Zone of Inhibition:

  1. Composition of medium
  2. Acidic pH of media
  3. Alkaline pH of media
  4. Reading of zones
A
  1. Affects rate of growth, diffusion of antibiotics and activity of antibiotics
  2. Tetracycline, novobiocin, methicillin zones are larger
  3. Aminoglycosides, erythromycin zones are larger
  4. Subjective errors in determining the clear edge
51
Q

E-Test

A

MIC is the point where the zone of inhibition intersects the strip
The strip has a gradient of antibiotics on it, place on bacterial lawn, measure

52
Q

Broth dilution method

A

Permit quantitative results
Indicates concentration of drug necessary to inhibit or kill the microorganisms tested
Doubling dilutions of antibiotic in broth
Turbidity visualization = MIC
Grow non turbid tubes, growth overnight = MBC

53
Q

What broth is usually used?

A

Muller-Hinton

54
Q

Agar dilution method

A

Permit quantitative results
Indicates concentration of drug necessary to inhibit or kill the microorganisms tested
Doubling dilutions of antimicrobial agent in incorporated agar media
One concentration of antibiotic/plate, several different strains/plate

55
Q

What is the replicating inoculator device called that is used for the agar dilution method?

A

A Steers-Foltz replicator

It delivers 0.001 mL of bacterial inoculum

56
Q

Vitek

A

Automated system

Doesn’t work well for organisms that are harder to grow (need special conditions, etc)

57
Q

Which drug classes are good for treating atypical pathogens?

A

Fluoroquinolones
Macrolides
Tetracyclines

58
Q

Beta lactams should not be used on patients with..

A

Immediate hypersensitivity reaction history

59
Q

What 3 bacteria NEED combination therapy

A

Mycobacterium tuberculosis
S aureus
H pylori

Clinical Microbiology (25 decks)

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