Antimicrobial PKPD

what dictates Cmax

PK

what dictates MIC

PD

what dictates %T

PK

what dictates AUC

PK

key parameter associated with penicillin’s, cephalosporins, carbapenems, macrolides, oxazolidinones

%T > MIC

key parameter for aminoglycosides

Cmax:MIC

key parameter for quinolones

AUC:MIC

key parameter for vancomycin, azithromycin, and tetracycline

AUC:MIC

pattern for penicillins, cephs, carbapenems, macrolides, and ozaxolidiones

time-dependent killing, minimal/moderate persistent effects

pattern for aminoglycosides and quinolones

concentration-dependent, prolonged persistent effects

pattern for vanco, azithro, and tetra

time-dependent, prolonged persistent effects

dosing goals for penicillin, cephs, carbapenems, macrolides, oxazolidiones

prolonged infusion time, continuous infusion, shorter dosing interval, increase dose

dosing goals for aminoglycosides and quinolones

extended interval dosing, maximize safe dose

dosing goals of vanco, azithro, tetra

optimize safe dose

what are the three indices controlling how good an antibiotic will work?

%T>MIC, AUC:MIC, Cmax:MIC

each PKPD indices can be optimized by controlling:

dose, infusion time, and dosing interval

disease-related changes that can affect PK

pH (changes drug ionization), organ blood flow (changes drug clearance), fluid shifts (changes in Vd), and changes in albumin (changes in free drug)

when patients have impaired clearance (low Vd) what happens to drug concentration?

increased

when patients have increased clearance (high Vd) what happens to concentration?

decreases

T/F: disease states are much stronger indicators of drug concentrations than kidney function

true

when there is decreased cardiac output how is PK affected

reduced clearance

when capillary leakiness increases how is PK affected?

increased Vd

when a patient has AKI and hyperfiltration how is PK affected

increased clearance

when a patient has chronic kidney injury how is PK affected?

reduced renal clearance

which antibiotics do not need renal dose adjustments?

ceftriaxone, clindamycin, oxacillin, moxifloxacin, metronidazole, azithromycin, nafcillin, doxycyline, erythromycin, dalfopristin/quinupristin, tigecycline, linezolid, ciprofloxacin

when antibiotics are not enough what is done?

go in and remove the bugs: abscess drainage, prosthetic removals, debridement of necrotic tissue, injection of medication into ventricles of brain if med can’t pass BBB

which type of bacteria cause less serious infections and are more common?

gram positive aerobes

which type of bacteria have a significant barrier to a number of antibiotics?

gram negative aerobes

which type of bacteria are wimpy and normally not a clinical problem?

gram positive anaerobes

which type of bacteria is being referenced when they say “covering anaerobes”

gram negative anaerobes

what is MALDI-TOF

mass spectrometry technique (detects proteins)

what is PCR-based technique

detects genes

T/F: MICs should be interpreted as either susceptible, intermediate, or resistant, not based on how big or small the number is

true

what is the target for vancomycin

AUC_24,ss : MIC > 400 mg*h/L

what factors control achieving the vanco goal of AUC_24,ss : MIC > 400 mg*h/L

Cl (of patient), dose₂₄ (daily dose), and MIC (of bacteria)

Dose=

AUC * CL

An AUC:MIC is dependent on which factors?

the daily dose a patient receives, the pateint-specific clearance, and the bacterial-specific MIC

what is the worst way to determine patient-specific clearance?

trough measurements

what is the best way to determine patient-specific clearance

Bayesian estimation of clearance