a) Interpret the three pharmacodynamic (PD) profiles, labelled Scenario 1, Scenario 2 and Scenario 3, shown below. (40% marks)
b) For each PD profile, describe how you would optimise the dose and/or frequency of antibiotic if prescribing:
i) a beta lactam
ii) an aminoglycoside
Methods to optimise:
(i) Beta Lactam agents:
Obviously, in Scenario 1 the antibiotics will never be effective as the MIC is never achieved, and in Scenario 2 the antibiotics will kill the bugs shortly before they kill the patient with toxicity. In Scenario 3, one might argue that nothing needs to change for antibiotics with concentration-dependent killing; whereas those with time-dependent killing should probably be dosed more regularly (or given as an infusion).
This would work best as a table:
|Drug profile||Time-dependent killers||Concentration-dependent killers|
|MIC not achieved||Increase dose
Decrease dosing interval
|Dose accumulation||Decrease dose
Increase dosing interval
|Increase dosing interval|
|MIC achieved but prolonged sub-MIC time||Decrease dose AND increase dosing frequency||Do nothing (fine like this)|
In regard to the college answers, one might add that "continuous infusion" is the correct answer to any sort of dose adjustment problem when it comes to time-dependent killers, and "therapeutic drug monitoring" can never be a wrong answer in a dose adjustment question. Kill characteristics of antibiotic agents are discussed elsewhere.