Antimicrobial Pharmacodynamics

Question 1

What is Pharmacodynamics?

Answer 1

• Wanting to see the effects of the drug and there MOA

Question 2

What are we looking at for b-lactam pharmacodynamics?

Answer 2

• Penicilins, Cephalosporins, Carbapenems, Monobactams
• **Time that free drug concentration remain above the MIC [fT>MIC]

Question 3

What are some of the Antibacterial Properties in b-lactam Pharmacodynamics?

Answer 3

• NOT rapidly bactericidal
• Time Dependent Bactericidal
• NO PAE [only in carbapenems & Gram +]

Question 4

What values are we looking at when trying to Maximize fT>MIC in b-lactam Pharmacodynamics?

Answer 4

• Gram Neg: Carbapenems >40%; Penicillins >50%; Cephalosporins >60%
• Gram Pos: >40-50%

Question 5

What are some of the strategies to Maximize fT>MIC in b-lactam Pharmacodynamics?

Answer 5

• Increase Dose [increases half life]
• Shorter Interval [More often = good]
• Continuous Infusion
• Prolonged Infusion

Question 6

When talking about optimization of antibiotic therapy for HAP/VAP, what is important to know regarding b-lactam Pharmacodynamics?

Answer 6

• Do Continuous or Prolonged
• Decreased Mortality & LOS with Increased cure rate

Question 7

What are we looking at for Fluoroquinolone Pharmacodynamics?

Answer 7

• “-floxacin”
• fAUC0-24/MIC Ratio

Question 8

What are some of the Antibacterial Properties for Fluoroquinolone Pharmacodynamics?

Answer 8

• Rapidly Bactericidal
• Concentration Dependent
• PAE effect for BOTH Gram +/-

Question 9

When looking at human data for the Fluoroquinolones Pharmacodynamics, what is important to understand about AUC?

Answer 9

• Should be around 125-250 to have a good affect

Question 10

What are the desirable targets for Fluoroquinolone Pharmacodynamics?

Answer 10

• Gram Neg: >100
• Gram Pos: > 30-40
• CAVEATS: Cipro ~125 & Levo ~87

Question 11

What are we looking at for Aminoglycoside Pharmacodynamics?

Answer 11

• Peak/MIC Ratio [8-10:1]
• Maybe AUC/MIC [Serious = 80-100 & Non-Serious = 30-50]

Question 12

What are some of the Antibacterial Properties for Aminoglycoside Pharmacodynamics?

Answer 12

• Rapidly Bactericidal
• Concentration Dependent
• PAE effect for BOTH Gram +/-
• Adaptive Resistance

Question 13

What is Adaptive Resistance in Aminoglyoside Pharmacodynamics?

Answer 13

• The down regulation of anioglycoside transport into bacteria when no free drug exist [basically as long as you have detectable drug - is uses the transport which the bacteria can stop]

Question 14

What are we looking at for Vancomycin Pharmacodynamics?

Answer 14

• Time Dependent, LONG PAE for Gram +
• AUC0-24/MIC

Question 15

What is the goal AUC/MIC for Vancomycin Pharmacodynamics?

Answer 15

• AUC/MIC ~ 400-600 [Asseming MIC = 1]

Question 16

What was important to understand the PROVIDE Trial as it relates to Vancomycin Pharmacodynamics?

Answer 16

• Prospective
• Primary outcome was FAILURE and Secondary Outcome was AKI; SO high Vancomycin Doses were associated with AKI
• Why we do ~515 AUC average

Question 17

What are some of the other important medications Pharmacodynamics?

Answer 17

• Aminoglycosides: Concentration Dependent; Peak/MIC,AUE/MIC
• b-lactams: Time Dependent; T>MIC
• Daptomycin: Concentration Dependent: AUC0-24/MIC, Peak/MIC
• Fluoroquineolones: Concentration Dependent, AUC0-24/MIC
• Vancomycin: Time Dependent; AUC0-24/MIC