Lecture 05 - Antibiotics and Antifungals Flashcards

1
Q

Why do we monitor antimicrobial drug levels

A

optimize serum levels, minimize toxicity, research

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2
Q

Why does vancomycin fit the need to do TDM

A

narrow therapeutic window (lacks effectiveness below 10 mg/L but toxic if troughs are greater than 20 mg/L

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3
Q

How does vancomycin work

A

inhibits bacterial cell wall synthesis and used to treat resistant Gram positive organisms

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4
Q

Why is vancomycin not ideal

A

it is a large molecule which makes it hard to pass across cell membranes making it difficult to penetrate site of infection

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5
Q

What does time dependant bacterial kill mean

A

exposure over time is important

the ratio between area under a curve and MIC (trough levels 4-6X MIC is ideal)

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6
Q

What does inoculum dependant mean

A

less effective with larger inoculum, aggressive therapy may be warranted

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7
Q

What are the signs of vancomycin toxicity

A

red neck syndrome, nephrotoxicity

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8
Q

How is vancomycin monitored

A

usually with a blood draw just before the 5th dose (trough) to ensure levels are okay

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9
Q

What patients should more frequent vancomycin levels be considered

A

deteriorating or unstable kidney function, morbidly obese, therapy lasting >2 weeks, infants/children with serious infections, CSF infections, CF/Burn patients, dialysis patients

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10
Q

Why do aminoglycosides meet the criteria for TDM

A

very toxic

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11
Q

What do you measure to ensure aminoglycosides are dosed appropriately

A

peaks for afficacy, troughs for toxicity

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12
Q

What is the ideal dosage for aminoglycosides

A

high dose followed with recovery time before next dose

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13
Q

What are the adverse effects of aminoglycosides

A

nephrotoxicity, ototoxicity

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14
Q

What are risk factors of aminoglycosides

A

unadjusted doses, duration of treatment, hypovolemia, hypotension, other nephrotoxic/ototoxic drugs

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15
Q

When does nephrotoxicity generally occur during treatment with aminoglycosides

A

5-7 days into treatment

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16
Q

When does vestibular autotoxicity usually occur during treatment with aminoglycosides

A

5-14 days into treatment

17
Q

What is extended interval dosing

A

employs the principals of concentration dependant kill and drug free intervals

18
Q

When would we not want to use extended interval dosing

A

endocarditis, dialysis patients, CF patients

19
Q

What is the hartford nonogram method

A

used to estimate intervals of administration of aminoglycosides, a draw is taken x time after administration and then the drug concentration is plotted as a product of time to see where on the graph it falls

19
Q

What is post-antibitic effect

A

the time after drug falls below MIC but is still effective

20
Q

What is the trough method for dosing of aminoglycosides

A

measures the trough to ensure the drug is undetectable

21
Q

What is the risk with the trough method

A

its hard to know how long the drug has been undetectable (should we have checked sooner?)

22
Q

What are the three classes of antifungals

A

polenes, echinocandins, new triazoles

23
Q

What is amphotericin

A

an antifungal that is toxic and could qualify for TDM except it cannot be monitored with blood/serum levels

24
Q

What is voriconaole

A

a non linear antifungal effective against yeast and mould that has increasing evidence of toxicity

25
Q

What is the half life of voriconaole

A

6-12 hours

26
Q

What is the therapeutic index of voriconaole

A

1.0 mcg/nL - 5.5 mcg/mL

27
Q

What metabolizes voriconaole

A

CYP2C19, CYP2C9, CYP3A4

28
Q

What causes intra/inter patient variability with voriconazole

A

saturable hepatic enzyme clearance, age, drug-drug interactions, variability in absorption or hepatic clearance with dysfunction, genetic polymorphisms of CYP2C19

29
Q

What are some antifungals where TDM are used

A

itraconazole, posaconazole, isacuconazole