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
(60% marks)
a)
Comments:
Scenario 1
Scenario 2.
Scenario 3
b)
Methods to optimise:
(i) Beta Lactam agents:
Scenario 1
Scenario 2
Scenario 3
(ii) Aminoglycosides
Scenario 1
Scenario 2
Scenario 3
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 |
Increase dose |
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.