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Clinical Microbiology > Antibiotics > Flashcards

Antibiotics Flashcards

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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

Study These Flashcards
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
Fluoroquinolones
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
Two enzymes fluoroquinolones target
DNA gyrase Topoisomerase 4 Inhibit DNA synthesis
27
Qnr
Binds to protein and protects DNA gyrase from binding of the antibiotic
28
Main adverse effect of fluoroquinolones
Cartilage toxicity/ tendon rupture | Restrict pediatric usage
29
Metronidazole
Go to anaerobic drug | Works by damaging DNA - inhibits nucleic acid synthesis
30
3 benefits of metronidazole
Bioavailable - can take orally Very little resistance Cheap
31
4 main classes of drugs that inhibit protein synthesis
1. MLS (macrolides, lincosamides, streptogramins) 2. Tetracyclines 3. Aminoglycosides 4. Linezolid
32
3 drugs in the macrolide class
Erythromycin Clarithromycin Azithromycin
33
Macrolides
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
2 mechanisms of macrolide resistance
``` Efflux pump (M phenotype) Target site modification erm (MLS phenotype) ```
35
Clindamycin
Anaerobic Gram positives Doesn't work well against gram negatives Associated with C difficile colitis
36
Tetracyclines
Tetracycline, Doxycycline, Minocycline Bind reversibly to the 30S ribosomal subunit Really good against atypical Discolouration of teeth
37
Aminoglycosides
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
Why cant you use aminoglycosides to treat anaerobic infections or abscesses?
They have to be actively transported into the bacterial cell – requires oxygen for transport
39
What is the most common form of resistance for aminoglycosides?
Enzymatic modification
40
2 adverse effects of aminoglycosides
Ototoxic | Nephrotoxic
41
Colistin
Gram negative agent with some gram positive activity Also called polymyxin Relatively toxic Disrupts outer membrane
42
Daptomycin
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
The beta-haemolytic strep are NEVER resistant to...
Penicillin or any beta lactam
44
Enterococcus are all intrinsically resistant to what class of drugs?
Cephalosporins | ALWAYS
45
E. cloacae and Citrobacter can have inducible resistance to what type of drugs?
Beta lactams
46
Nitrocephin disks
Quick screen for beta-lactamase production Nitrocephin is a cephalosporin When you break open the beta lactam ring it changes color
47
The Kirby-Bauer Test
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
Factors Affecting Size of Zone of Inhibition: 1. Inoculum density 2. Timing of disc application 3. Temperature of incubation 4. Incubation time
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
Factors Affecting Size of Zone of Inhibition: 5. Depth of the agar medium 6. Proper spacing of the discs 7. Potency of antibiotic discs
5. Thin media yields excessively large inhibition zones and vice versa 6. Avoids overlapping of zones 7. Deterioration in contents leads to reduced size
50
Factors Affecting Size of Zone of Inhibition: 8. Composition of medium 9. Acidic pH of media 10. Alkaline pH of media 11. Reading of zones
8. Affects rate of growth, diffusion of antibiotics and activity of antibiotics 9. Tetracycline, novobiocin, methicillin zones are larger 10. Aminoglycosides, erythromycin zones are larger 11. Subjective errors in determining the clear edge
51
E-Test
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
Broth dilution method
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
What broth is usually used?
Muller-Hinton
54
Agar dilution method
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
What is the replicating inoculator device called that is used for the agar dilution method?
A Steers-Foltz replicator | It delivers 0.001 mL of bacterial inoculum
56
Vitek
Automated system | Doesn't work well for organisms that are harder to grow (need special conditions, etc)
57
Which drug classes are good for treating atypical pathogens?
Fluoroquinolones Macrolides Tetracyclines
58
Beta lactams should not be used on patients with..
Immediate hypersensitivity reaction history
59
What 3 bacteria NEED combination therapy
Mycobacterium tuberculosis S aureus H pylori

Clinical Microbiology (25 decks)

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