Slides from the WHO Italian CME Antimicrobial stewardship 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.

1. Pharmacology Of Antimicrobials
for Clinicians: Select Topics
PART 2

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.
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3. BIOAVAILABILITY & ORAL
ANTIMICROBIALS
Key concept #1:
Core Competencies 1, 2, 3 & 5
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4. EXTENDED INFUSION
Key concept #2:
Core Competencies 1, 2, 3 & 5
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5. Drug properties
Pharmacokinetics (PK)
• What the body does to the drug
Pharmacodynamics (PD)
• What the drug does to the body and microorganism
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6. Drug properties
Pharmacodynamics (PD)
• Bacterial killing
• Concentration-dependent
• Time-dependent
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7. Drug properties
Pharmacodynamics (PD)
• Bacterial killing
• Concentration-dependent
• Time-dependent
• Post-antibiotic killing
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8. Antibiotic
Concentration
Time (hour)
Concentration dependent activity
Optimal use:
Large, infrequent dosingMIC
Maximum
concentration
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9. Antibiotic
Concentration
Time (hour)
Time dependent activity
Optimal use:
Optimize duration of
exposure
MIC
Time above
MIC
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10. Antibiotic
Concentration
Time (hour)
Time dependent activity
MIC
Time above
MIC
Minimum inhibitory
concentration (MIC)
= lowest concentration
that inhibits growth
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11. Minimum inhibitory concentration (MIC)
• Lowest concentration of an
antimicrobial that inhibits
visible growth in vitro
• Reference microbiology
organizations provide
interpretive guidelines
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WHO/O. Karatuna

12. MIC breakpoints Urine culture: E. coli
WHO/O. Karatuna
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MIC breakpoints

13. https://www.youtube.com/watch?v=5cun8wdX0Us
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14. Antibiotic
Concentration
Time (hour)
Time dependent activity
Optimal use:
Optimize duration of
exposureMIC
Time above
MIC
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15. 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
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16. Antibiotic
Concentration
Time (hour)
Time dependent activity
Strategy (infusions):
• Frequent
• Extended
• Continuous
MIC
Time above
MIC
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17. Urine culture #2: E. coli
WHO/O. Karatuna
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18. Antibiotic
Concentration
Time (hours)
Time
above
MIC
MIC
Dose Dose
Beta-lactams: time dependent killing
MIC
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19. Antibiotic
Concentration
Time (hours)
Time
above
MIC
MIC
Dose Dose
Beta-lactams: time dependent killing
MIC
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20. Antibiotic
Concentration
Time (hours)
Time
above
MIC
Dose Dose
Beta-lactams: extended infusion
MIC
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21. Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
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22. Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
Highly bioavailable oral
antibiotics are those that
achieve serum concentrations
comparable to antibiotics
administered intravenously.
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23. 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.
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24. Review: Pharmacology for Clinicians
Drug
Dose
Duration
Route
prescription
.............
.............
.............
PK/PD can optimize use of
antimicrobials
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25. Quiz time!
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proceed.