lowest drug concentration without visible growth for 16-20 hours at 35 degree celsius
Does MIC mean that the bacteria is all eradicated?
Nope
it is the drug concetnration that results in stasis
What is MIC50?
50% of inhibition of inoculum.
we usually use MIC90
Does MIC inform the potency of antimicrobial activity?
Yes
Does MIC inform the time course of antimicrobial activity?
Nope
Does MIC inform growth inhibitory effects that may persist after antimicrobial exposure?
Nope
If MIC is low, what does this mean?
the bug is sensitive
the higher the number, the more antibiotic you need
For MIC, how much fold of antibiotic dilution do you add? how long do you incubate the tube?
2 fold
18-24 hours
Does ceftriaxone cover pseudomonas?
Nope
Which bacteria depends less on the host immune system?
cidal vs. static
cidal
PCN is bactericidal or static?
bactericidal
inhibit cell wall/memb
cephalosporin is bactericidal or static?
cidal
inhibit bacteria cell wall/memb
FQ is bactericidal or static?
cidal
interfere with bacterial enzymes
sulfa abx is bactericidal or static?
static
inhibit protein synthesis
tetracycline is bactericidal or static?
static
inhibit protein synthesis
linezolid is bactericidal or static?
static
inhibit protein synthesis
How does toxin production work in bactericidal activity? How should you manage?
sudden lysis of bacteria leads to a sudden increase in bacterial products and this stimulate cytokine production
this can be harmful to the host and cause inflammation
co-administer steroids in meningitis
add bacteriostatic agents because they directly inhibit the production of toxin (clindamycin)
What regimen do you give for meningitis?
must give abx adn steroid together on day 1 because of toxin production and inflammation
What regimen do you give for PCP in HIV patients?
Bactrim for 21 days + steroid taper
What kind of bacteria does clindamycin cover?
gram positive
anaerobe
inhibit toxin production
when would you choose cidal antibiotics?
endocarditis, meningitis, osteomyelitis
immunocompromised patietns
Can you use moxifloxacin for UTI?
Nope
Enterococcal endocarditis does not have much cidal agents for us to use. What would you do?
use synergy
aminoglycoside + b-lactams
When is the combination of tetracycline and b-lactams good?
this is a trick question
they antagonize each other
cidal agents work only when the cells are duplicating so don't combine cidal and static
what is the definition of pharmacodynamic?
describes the relationship between measurements of drug exposure in serum, tissues and body fluids and the pharmacologic and toxic effects of the drug.
What is Cmax/MIC?
ratio of highest concentration attained in a dosing interval to the MIC
what is AUC/MIC?
ratio of measure of the total exposure of drug to the MIC
what is %T>MIC?
time that drug concentration exceeds MIC. stated as a percentage of the dosing interval.
Explain how concentration dependent abx should do in terms of MIC.
need high MIC
Explain how time dependent abx should do in terms of MIC.
need to stay above MIC for the dosing interval at least 60-80% of the time.
What is post antibiotic effect?
persistent inhibitory effect on a bug that results from drug exposure after drug has been completely removed.
delay before microorganism recover and reenter a log growth period
this is only in concentration dependent abx.
Is PAE seen in concentration dependent abx?
Yes
not time dependent
Is PAE seen in time dependent abx?
Nope
just in concentration dep abx
PAE depends on what factors?
influences
bacteria
inoculum size
concentration antibiotic
duration of exposure
A: peak/MIC (Cmax/MIC)
B: AUC/MIC
C: Time > MIC
D: sub-MIC
E: PAE
What kind of effects does concentration dependent abx have?
moderate and prolonged persistent effects
Rate and extent of bactericidal action increases with ____ (inc/dec) drug concentration for concentration dependent abx.
increasing
What is the goal for concentration dependent abx? Explain in terms of pharmacodynamic terms.
maximize concentration
AUC/MIC and peak/MIC
Aminoglycoside
concentration or time dependent?
conc
FQ
concentration or time dependent?
conc
ketolides (telithromycin)
concentration or time dependent?
conc
metronidazole
concentration or time dependent?
conc
amphotericin B
concentration or time dependent?
conc
daptomycin
concentration or time dependent?
conc
High dose extended interval for AG optimizes PD concentration dependent killing in treatment of what kind of infection?
gram negative infections
what is gentamycin dosing for extended interval dosing?
5-7mg/kg/day
what is tobramycin dosing for extended interval dosing?
5-7mg/kg/day
what is amikacin dosing for extended interval dosing?
15-20mg/kg/day
What is the goal for extended interval dosing for AG in terms of peak and trough?
to have high peaks
and UNDETECTABLE troughs
Does high dose extended interval AG have PAE?
yes post antibiotic effect
What is the benefit of high dose extended interval AG compared to traditional dosing?
less nephrotoxic: saturable transport system regarding uptake of drug in the kidney (kidneys can only absorb max amount per time so qd is better than more often). less frequent single daily dose may minimize accumulation (drug free interval).
ototox is uncertain
What should the trough of high dose extended interval dosing AG be?
UNDETECTABLE!
What should the trough of traditional dosing AG be?
<2mg/L for gent and tobra
<10mg/L for amikacin
what is the synergy dosing for gentamycin? what should the trough be?
1mg/kg q8h
trough: <1
When a resident asks you if the trough for AG is okay, what should you question?
need to know what dosing interval was used
need to know if it was used for synergy for Gram positive
When should you sample extended interval dosing AG (peak and trough) troigu? how does it accumulate?
no significant accumulation
trough: measurement can be obtained after any dose
peak: no need to measure peak
how do you infuse traditional dosing AG? when do you draw peak and trough?
infuse over half hour, wait one half hour
then draw peak
trough drawn before next dose (or within half hour of dose)
What are key pharmacodynamic parameters for AG?
peak/MIC ratio (unlike in FQ, peak is used here because AG loves water so it doesn't go into CNS and cause CNS tox)
AUC/MIC ratio or AUIC
AUC24= 70-100mghr/L
What is AUC formula?
AUC = dose / clearance
What are key pharmacodynamic parameters for fluoroquinolone? (what are target numbers?)
AUC/MIC ratio (125-250)
peak/MIC ratio is NOT used because if the peak is high, CNS issue
Is ciprofloxacin good for S. pneumo?
not really
levofloxacin is better
For FQ, what AUC:MIC ratio is good for gram negative rods?
> 125 for gram negative
For FQ, what AUC:MIC ratio is good for gram positive cocci?
>30 for gram positive
The higher the MIC, how much drug would you need?
MORE drug
Extent of bacterial killing for time-dependent bacteria depends on the ____.
time the active drug cnocentration remains above the MIC.
What kind of effect does time dependent abx have?
mild/moderate persistent effect
Beta lactams
concentration or time dependent?
concentration or time dependent?
time
macrolides (azithromycin, clarithromycin, erythromycin)
concentration or time dependent?
time
clindamycin
concentration or time dependent?
time
Oxazolidionones (linezolid)
concentration or time dependent?
time
flucytosine
concentration or time dependent?
time
Which time dependent abx has prolonged persistent effect, as opposed to minimal/moderate persistent effect?
Azithromycin
Tetracycline
Glycopeptide (vancomycin, televancin)
Q/D (quinupristin dalfopristin)
fluconazole
Tetracycline
concentration or time dependent?
time
Glycopeptides (vancomyin, televancin)
concentration or time dependent?
time
Q/D
concentration or time dependent?
time
fluconazole
concentration or time dependent?
time
What is the goal for time dependent abx?
optimize duration of exposure (time >MIC)
What is the benefit of continuous infusion over intermittent for time dependent abx?
therapeutic efficacy
because do not need to give as much drug: cost saving - amount drug/time; reduced risk of dose related toxicity
What are problems of continuous infusion for time dependent abx?
stability at room temperature
no drug free interval so adverse reaction
access (for other drugs etc)
What is the extended infusion dosing for Zosyn?
3.375g IVPB TRO 4 hours q8h (>40ml/min), q12h (10-39ml/min)
what does APACHE stand for?
acute physiologya nd chronic health evaluation
assess risk of mortality
What should fT>MIC be for time dependent abx to be good?
50-70%
Vancomyin failures have been observed when MIC is ____mg/L.
1-2mg/L
What should we monitor in vancomycin?
check trough
peak is not necessary
what does penetration into tissue for vancomycin depend on?
affected by inflammation and disease state
i.e.)
meningitis: higher penetration if inflamed
DM: lower penetration in diabetics
what is the MIC for vancomyin?
1-2mg/L
what should vancomycin trough be?
15-20mg/L
what is the relationship between trough and MIC for vancomycin in in patients with MRSA infection?
trough is 4x MIC in patients with MRSA
When would you use high trough of vancomycin?
20mg/L
osteomyelitis, endocarditis, bacteremia
What should the target AUC/MIC for vancomycin be for MRSA?
>400
What do you use to dose vancomycin?
nomogram (many are outdated)
patient specific
use actual body weight
What is the loading dose for vanco? why is it needed?
25-30mg/kg (~2g)
vanco Css is reached within 24-48 h but many need LD because of clinical status.
what is the infusion rate for vancomyin?
15mg/min
How do you infuse vancomycin? (in terms of rate and dose?)
if >1g, divide by 15mg/min for the rate
if <1g, infuse 1g over an hour.
What should you do for monitoring for vancomycin for critically ill patient?
attain target trough earlier
what is the dosing strategy of vanco for patients with normal renal function?
may load 25-30mg/kg (~2g)
then 15-20 mg/kg q8-12h
If the patient's condition is too serious (i.e. SICU), what should you do for vancomycin treatment?
1) may consider daptomycin
2) increase vancomycin level but check trough q4 day and check creatinine
Is ototoxicity for vancomycin common?
rare
usually seen in patients receiving other ototoxic agents (i.e. gent)
how do you assess vancomyin nephrotoxicity?
>0.5mg/dL over baseline or increase of 50% for 2 consecutive assays.
what are risk factors for nephrotoxicity for vanco?