17 Antimicrobial PK/PD Beringer Flashcards
What is the definition of Pharmacokinetics (PK)?
Characterization of absorption, distribution, metabolism, elimination. Quantification of the amount and time course of a compound within the body
What is the definition of Pharmacodynamics (PD)?
Examines relationship between drug concentration vs. time and the rate and extent of antimicrobial effect at the site of infection
How is antimicrobial activity measured for individual antibiotic activity?
MIC/MBC. Bactericidal rate vs. drug concentration. Persistent effects (e.g. PAE)
How is antimicrobial activity measured for combination therapy?
Specialty lab tests. Serum bactericidal titer (SBT). Synergy testing (checkerboard)
What is the MIC/MBC ratio?
Antibiotic concentration at which growth of the majority of a standard population of bacteria is inhibited (MIC) or killed (MBC). Inoculum size used: 1x10^6 (might not relate accurately in vivo). Laboratory conditions for growth (pH, aerobic environement, exponential phase) may not translate in vivo. Continuous exposure to fixed drug concentration in lab might not translate well in vivo d/t fluctuating levels in vivo
What is MIC/MBC best used for?
Acute infections, not chronic
For concentration vs. bactericidal rate, what is Time-Dependent Killing?
Bactericidal activity saturable at concentrations of 4-5 times the MIC (i.e. B-lactams). Multiple doses/day to keep stead level
For concentration vs. bactericidal rate, what is Concentration-Dependent Bactericidal Activity?
Killing increases linearly with increasing antibiotic concentrations (i.e. Aminoglycosides). High dose used QD
Which drug class doesn’t benefit from a high peak concentration?
No advantage in B-lactams, just causes more ADRs
What do In-Vitro persistent effects depend on?
Type of organisms. Type of antimicrobial agents. Concentration of antimicrobial. Duration of exposure
What are some In-Vivo measures of persistent effects?
Postantibiotic Leukocyte Enhancement (PA-LE). Postantibiotic Sub-MIC Effect (PA-SME)
What is the In-Vitro measure of persistent effects?
Postantibiotic Effect (PAE): persistent suppression of bacterial growth after short exposure to antibiotics
How do PAEs compare in-vivo and in-vitro?
In-vivo PAE are 3-4x longer than reported in-vitro. Persistent effects exposure dependent (PAE for aminoglycosides increases proportionally with AUC)
What is Type I Pattern of Activity for Antimicrobials?
Concentration-dependent killing and moderate-prolonged persistent effects
What are the goals of therapy for Type I Pattern of Activity?
Maximize concentrations
What are the PK/PD parameters for Type I Pattern of Activity?
Dependent on 24h-AUC/MIC. Peak/MIC
What is Type II Pattern of Activity for Antimicrobials?
Time-dependent killing and minimal persistent effects
What are the goals of therapy for Type II Pattern of Activity?
Maximize duration of exposure
What are the PK/PD parameters for Type II Pattern of Activity?
T > MIC (time above MIC)
What is Type III Pattern of Activity for Antimicrobials?
Time-dependent killing and moderate-prolonged persistent effects
What are the goals of therapy for Type III Pattern of Activity?
Maximize amount of drug
What are the PK/PD parameters for Type III Pattern of Activity?
24h-AUC/MIC
What antibiotics have Type I Pattern of Activity?
Aminoglycosides! FQs. Metronidazole. Daptomycin. Ketolides. Amphotericin B
What antibiotics have Type II Pattern of Activity?
B-lactams. Macrolides. Oxazolidinones. Flucytosine
What antibiotics have Type III Pattern of Activity?
Vancomycin. Azithromycin. Clindamycin. Streptogramins. Tetracyclines
What are the PK/PD goals for Aminoglycosides?
Peak/MIC > 10, AUC24 70-100
What are the PK/PD goals for Quinolones?
AUC24/MIC > 125 (P. aeruginosa), > 30-50 (S. penumoniae)
What are the PK/PD goals for Vancomycin?
Maximize T>MIC, AUC24/MIC > 400 (?)
What are the PK/PD goals for B-Lactams?
T>MIC > 40-50%, > 100% for some severe infections
What type of dosing do you want to use for Aminoglycosides?
Extended interval dosing