A short presentation about the difference in pharmacodynamics of concentration-dependent vs. time dependent antibiotics and the clinical implications of this phenomenon.

1. Optimal Antibiotic Dosing
The Pharmcokinetic-Pharmacodynamic Interface
Hasan Arafat, M.D
Resident Physician, Internal Medicine
Augusta Victoria Hospital

2. Introduction
• Antibiotics can be classified according to their pattern of antimicrobial
activity into to classes:
• Concentration-dependent killing
• Time-dependent killing
• Hybrid pattern

3. Introduction
• Concentration-dependent killing: the higher the drug concentration
relative to pathogen MIC, the greater the rate and extent of
antimicrobial activity
• Time-dependent killing: the duration of exposure determines the
antimicrobial activity
• Hybrid pattern: antimicrobial activity is dependent on the duration of
exposure with a prolonged, persistent post-antibiotic effect

4. Concentration-Dependent Antibiotics
• Bactericidal effect is directly proportional to the level of drug
• Associated with post-antibiotic effect:
• A phenomenon in which the bactericidal effect of a drug continues for a
period of time after the antibiotic level falls below the MIC
• Efficacy of these antibiotics is determined by the area under the curve
(AUC)
• A concentration of at least 10x MIC is needed for optimal effect

5. Time-Dependent Antibiotics
• Optimal activity is exerted when drug concentration is maintained
above MIC
• Typically, 2-4x MIC throughout the dosing interval
• Higher concentration does not result in greater killing
• No post antibiotic effect

6. MIC

7. AUC

8. Cmax
• the highest concentration of drug in the blood that is measured after
a dose. Cmax usually occurs within a few hours after the dose is
administered.

9. Pharmacological Indices of Antibiotic Activity
• Peak/MIC: ratio is defined as the /MIC) peak level divided by the MIC. It is
used to predict the efficacy of concentration dependent antibiotics.
• AUC/MIC is defined as the area under the AUC/MIC curve over 24 hours
divided by the MIC2. It is also used to predict the efficacy of concentration-
dependent antibiotics.
• T>MIC is defined as the cumulative T>MIC percentage of time over a 24
hour period that the drug concentration exceeds the MIC2. It is used to
predict the efficacy of time dependent antibiotics.
• Postantibiotic effect defined as persistent suppression effect of bacterial
growth after a brief exposure (1-2 h) of bacteria to an antibiotic even in the
absence of host defense mechanisms.