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Pharmacology Of Antimicrobials
for Clinicians: Select Topics
PART 2
Objectives
• Introduce basic concepts of
pharmacokinetics/pharmacodynamics of antimicrobials
• Describe oral bioavailability of antimicrobials
• Illustrate the concept of time-dependent antimicrobials
and describe optimizing the use of beta-lactam
antibiotics using prolonged infusion.
2
BIOAVAILABILITY & ORAL
ANTIMICROBIALS
Key concept #1:
Core Competencies 1, 2, 3 & 5
3
EXTENDED INFUSION
Key concept #2:
Core Competencies 1, 2, 3 & 5
4
Drug properties
Pharmacokinetics (PK)
• What the body does to the drug
Pharmacodynamics (PD)
• What the drug does to the body and microorganism
5
Drug properties
Pharmacodynamics (PD)
• Bacterial killing
• Concentration-dependent
• Time-dependent
6
Drug properties
Pharmacodynamics (PD)
• Bacterial killing
• Concentration-dependent
• Time-dependent
• Post-antibiotic killing
7
Antibiotic
Concentration
Time (hour)
Concentration dependent activity
Optimal use:
Large, infrequent dosing
MIC
Maximum
concentration
8
Antibiotic
Concentration
Time (hour)
Time dependent activity
Optimal use:
Optimize duration of
exposure
MIC
Time above
MIC
9
Antibiotic
Concentration
Time (hour)
Time dependent activity
MIC
Time above
MIC
Minimum inhibitory
concentration (MIC)
= lowest concentration
that inhibits growth
10
Minimum inhibitory concentration (MIC)
• Lowest concentration of an
antimicrobial that inhibits
visible growth in vitro
• Reference microbiology
organizations provide
interpretive guidelines
11
WHO/O. Karatuna
MIC breakpoints Urine culture: E. coli
WHO/O. Karatuna
12
MIC breakpoints
https://www.youtube.com/watch?v=5cun8wdX0Us
13
Antibiotic
Concentration
Time (hour)
Time dependent activity
Optimal use:
Optimize duration of
exposure
MIC
Time above
MIC
14
Antibiotic
Concentration
Time (hour)
Time dependent activity
Goal: drug
concentration > 4
times the MIC for
40%-60% of the
dosing interval
MIC
Time above
MIC
15
Antibiotic
Concentration
Time (hour)
Time dependent activity
Strategy (infusions):
• Frequent
• Extended
• Continuous
MIC
Time above
MIC
16
Urine culture #2: E. coli
WHO/O. Karatuna
17
Antibiotic
Concentration
Time (hours)
Time
above
MIC
MIC
Dose Dose
Beta-lactams: time dependent killing
MIC
18
Antibiotic
Concentration
Time (hours)
Time
above
MIC
MIC
Dose Dose
Beta-lactams: time dependent killing
MIC
19
Antibiotic
Concentration
Time (hours)
Time
above
MIC
Dose Dose
Beta-lactams: extended infusion
MIC
20
Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
21
Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
Highly bioavailable oral
antibiotics are those that
achieve serum concentrations
comparable to antibiotics
administered intravenously.
22
Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
Patients receiving IV
antimicrobials can often be
switch to oral antimicrobials to
complete a course of therapy.
23
Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
PK/PD can optimize use of
antimicrobials
24
Quiz time!
Please click
“Next” to
proceed.

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