Lecture 05 - Antibiotics and Antifungals Flashcards
Why do we monitor antimicrobial drug levels
optimize serum levels, minimize toxicity, research
Why does vancomycin fit the need to do TDM
narrow therapeutic window (lacks effectiveness below 10 mg/L but toxic if troughs are greater than 20 mg/L
How does vancomycin work
inhibits bacterial cell wall synthesis and used to treat resistant Gram positive organisms
Why is vancomycin not ideal
it is a large molecule which makes it hard to pass across cell membranes making it difficult to penetrate site of infection
What does time dependant bacterial kill mean
exposure over time is important
the ratio between area under a curve and MIC (trough levels 4-6X MIC is ideal)
What does inoculum dependant mean
less effective with larger inoculum, aggressive therapy may be warranted
What are the signs of vancomycin toxicity
red neck syndrome, nephrotoxicity
How is vancomycin monitored
usually with a blood draw just before the 5th dose (trough) to ensure levels are okay
What patients should more frequent vancomycin levels be considered
deteriorating or unstable kidney function, morbidly obese, therapy lasting >2 weeks, infants/children with serious infections, CSF infections, CF/Burn patients, dialysis patients
Why do aminoglycosides meet the criteria for TDM
very toxic
What do you measure to ensure aminoglycosides are dosed appropriately
peaks for afficacy, troughs for toxicity
What is the ideal dosage for aminoglycosides
high dose followed with recovery time before next dose
What are the adverse effects of aminoglycosides
nephrotoxicity, ototoxicity
What are risk factors of aminoglycosides
unadjusted doses, duration of treatment, hypovolemia, hypotension, other nephrotoxic/ototoxic drugs
When does nephrotoxicity generally occur during treatment with aminoglycosides
5-7 days into treatment
When does vestibular autotoxicity usually occur during treatment with aminoglycosides
5-14 days into treatment
What is extended interval dosing
employs the principals of concentration dependant kill and drug free intervals
When would we not want to use extended interval dosing
endocarditis, dialysis patients, CF patients
What is the hartford nonogram method
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
What is post-antibitic effect
the time after drug falls below MIC but is still effective
What is the trough method for dosing of aminoglycosides
measures the trough to ensure the drug is undetectable
What is the risk with the trough method
its hard to know how long the drug has been undetectable (should we have checked sooner?)
What are the three classes of antifungals
polenes, echinocandins, new triazoles
What is amphotericin
an antifungal that is toxic and could qualify for TDM except it cannot be monitored with blood/serum levels
