drraythe's version from 2016-04-29 14:59

intro and crap

Question Answer
"Best practice" is when you consider what 6 things when treating with abx?The right antibiotic, For the right patient, At the right dose, By the right route of administration, For the right duration, Without emergence of resistance
explain the "Best practice" S.P.A.C.E.D. approach (good approach to use when dealing with microbial infxn in animals)(1) SPECTRUM: is this drug effective against the pathogen? broad vs small spectrum. (2) PK/PD: can the drug get to the site of infection? CCD vs TDD (conc dependant versus time dependant). (3) Adverse reactions: is it safe to use this drug? (4) compliance: owner/regulatory, withdrawal times, ELDU (5) Environment: aerobe vs anerobe, acid versus base, presence of pus? (6) Diagnostics: susceptibility testing, breakpoints
if you want to see how effective a drug is against a certain pathogen, you'd look at what to compare them?MIC values
what are some drugs that just don't work in puss?potentiated sulfonamides, aminoglycosides
explain a little bit about how pH of drug affects how it moves through the bodyif it is an acid, it will go to more acidic places, and base to bases. If an acidic drug tries to go to a basic place in the body, it gets ionized and then is unable to pass the phospholipid bilayer of the cell and take effect in the cell (vice versa with base). Also note inflammation creates an acidic environment-- know this when choosing drugs. Also if you pick a basic drug to treat an infection (acidic environment) it will ionize and STAY there longer, also (keep in mind pKa and pH of site of infection)
what must you keep in mind when you are doing susceptibility testing?in vitro=/=in vivo. ex: rhodococcus equi is intracellular, so in culture certain abx (gentamycin) will kill it, but those abx have poor cell penetration, so its useless in vivo. Or susceptibility testing will say it's not very susceptible, but if it's a really localized infection, you can get the drug locally, might be able to get away with it (like sthing in eye or joint or lung-- reach high conc at target site)
what is a "breakpoint" in susceptibility testing?Zones of inhibition or MICs at which an organism is considered to be susceptible, intermediate, or resistant based on obtainable serum concentrations of the drug and clinical trials.
how do you know to pick the right ABX for the case at hand?look at the spectrum of activity, the bacterial susceptibility to it
2 things you need to carefully consider to help avoid resistancedose and duration of the abx
what should you consider if you want to make sure you got the right abx for the PATIENT?bactericidal versus bacteriostatic (is their immune system up for taking care of the bact after a static slows them down, or does the drug need to kill it for them?)... does the patient ACTUALLY require ABXs?
things you should consider if you want to make sure you have the right DOSE for your ptPK/PD modelling (using a group of dzd animals, and based on the cure rates, and the dosages we've used, try to match PK and PD to get the right result) time versus concentration dependent
if you wanna make sure you gave abx By the right route of administration, you should consider...(2)onset of action, pharmacokinetics (Vd aka volume of distribution)
what is PK/PD modelling?PK/PD (Pharmacokinetic/Pharmacodynamic) modeling (alternatively abbreviated as PKPD or PK-PD modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics.
what is Pharmacokinetics? is a branch of pharmacology dedicated to determining the fate of substances administered externally to a living organism. It attempts to discover the fate of a drug from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics describes how the body affects a specific drug after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of excretion of the metabolites of the drug
what is pharmacodynamics? the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect
List of the spectrum of action on the most common abx used in practice (pic)(red is truly broad spectrum abx)
what are the "truly" broad spectrum abx which kill G+, G-, anaerobic, and aerobic? (3)carbapenems, potentiated sulfonamides, doxycycline
what do potentiated penicillins kill?they kill G+ AND G-, but only aerobic ones and not anaerobic ones
(pic) chart of time dependant vs conc dependent killing abx
4 major chemical groups which are conc dependent killingfluoroquinolones (ex:enrofloxacin), aminoglycosides (ex: amikacin, streptomycin), nitroimidazoles (metronidazole) Polymixins (colistin) [so...FAP'N takes concentration]
what is an MIC?The lowest concentration of an antimicrobial agent that prevents visible growth of a microorganism on agar or in broth
what are the 3 groups of drugs which are duration of exposure AND conc dependanttetracyclines (oxytet, doxycycline), ketolides (azithromycin) glycopeptides (vancomycin) [so KGT instead of KGB wants ALL the things]
(7) time dependant abx (honestly just easier to remember the other two groups)penicillins, cephalosporins, macrolides+triamilides, lincosamides (clindamycin!), phenicols (chloramphenicol), sulfonamides, diaminopyrimidines (trimethoprim)
what is the PK-PD indices correlating with bacteriological effects for conc dependant abx? (basically letting you determine how high the dose should be)its AUC/MC (area under the curve divided by the minimum inhibitory concentration) (bigger curve= overall exposure of system to abx is bigger= bigger affect on bact at site of infection) or sometimes the maximum concentration divided by the MIC (Cmax/MIC) (dont bother to calc area under curve)...but AUC gives you better idea of overall exposure of antimicrobial
which group did he mention has a sig post-abx effect?the conc dependant ones-- bc you pass the MIC (minimal inhibitory conc) but still see effect in the animal (time dependant sometimes does and sometimes doesnt have post abx effect)
what is the PK-PD indices correlating with bacteriological effects for time dependant abx? (basically letting you determine how long the dose should be)T>MIC (only thing that matters is how long the conc stays above the MIC) (has to do with MOA-- need proliferating bact to kill them, whereas conc dependant just kills all the things)
the HEIGHT of the curve (PK/PD stuff) matters for which MOA?conc dependant (for time, only thing that matters is how long the conc stays above the MIC)
for the time AND conc dependant MOA abx, what is the PK-PD indices correlating with effect?it's AUC/MIC again (like conc dependant ones)
best practice: you should consider what, if you want to give abx for the right DURATION?consider time dependent versus concentration dependent killing
PK/PD: dose optimization depends on whether or not it is a dose or time dependant drug.yep
what is AUC? (not just what the acronym means) what does it tell us?area under the serum concentration time curve. Tells us about drug absorption and persistence
what is the AUC24/MIC ratio? what does it tell us?it is the area under the curve, over a 24hour period, and it predicts the efficacy of conc-dependent abx.
what is the cMAX?this is the peak conc in the plasma of the drug from its administration
what does the cMAX/MIC ratio predict?predicts efficacy of conc-dependent abx (but is less accurate than AUC/MIC)
what does T>MIC tell us?predicts the efficacy of time-dependant antibiotics (PAE- post abx effect- realize this can extend your dosing for a little bit)
explain this graph and how it relates to post-antibiotic effect BOTTOM Y AXIS: this is the ammpicillin conc in the plasma. TOP Y AXIS: this is the number of colony forming units (basically a measure of viable cells). At the top you can see it is comparing E. coli to Staph. aureus. What you see in the E. coli situation is that in the dosing interval, we see an increase in the number of bacteria- as we give the dose, the conc goes down and then the bact go back up again. So the infection keeps coming back-- meaning amicillin, for e coli, does not have a post-abx effect. So if it's a g- infxn, like ecoli, giving it every 8hrs is not going to be enough bc there is no PAE to cover your ass between doses. With Staph aureus though, you can see the MC is different (lower, prolly bc more effective on G+) and after giving the first dose, even if conc goes below MIC, we might not see further killing, but there is no enhanced growth of bact. so by the time we get the next dose, further dec bact. SO, with e coli when plasma conc of abx goes below MIC we see rapid prolif of bact, but we DONT with staph aureus-- which shows that ampicillin has post-abx-effect in S. aureus
if plasma concentration goes below MIC level, but you do not see proliferation of bacteria, what does this imply?post-abx effect is taking place