General drug pharmacodynamics

Pharmacodynamics (PD) describes the relationship between the concentration of the drug in the body and the effect seen; it is sometimes described as what a drug does in the body and in this case, the antibiotics are targeting bacteria and not our own cells.

Antimicrobial agents and PK/PD

Minimum inhibitory concentration (MIC)

The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible in vitro growth of a microorganism. It defines the in vitro levels of susceptibility or resistance of specific bacteria when applied to an antibiotic.

Area under the curve (AUC)

The blue-shaded area is the total amount of the antimicrobial in the plasma and is known as the area under the curve (AUC).

The graph below shows the concentration of an antimicrobial in the plasma over time. You can see the Cmax (peak concentration) and MIC for the target organism.

We will describe the importance of MIC, Cmax and AUC for antimicrobial agents next.

PK/PD properties

Antimicrobial agents can be split into these three different categories according to their PK/PD properties and how these relate to the MIC:

MIC and 24h – AUC/MIC.”>

• For concentration-dependent agents (Peak/MIC), there is a greater effect as the ratio of Cmax:MIC increases. For these agents, an increase in Vd will reduce the ability of the antimicrobial to reach a high Cmax. Conversely, a reduction in Vd will improve the ability of the antimicrobial to reach a high Cmax.
• For Time-dependent agents (T>MIC), the longer the duration of exposure is above the MIC, the greater the effect. Achieving higher concentrations does not result in greater efficacy, and the rate of bacterial killing is maximised at a low multiple of the MIC.
• For AUC:MIC ratio-dependent agents (24h – AUC/MIC), the efficacy of the antimicrobial depends on the ratio of the AUC:MIC. The AUC is determined by the total daily dose of antimicrobial.

Altering the dose of an antimicrobial mostly affects Cmax:MIC and AUC:MIC. Whereas altering the dosing interval affects AUC:MIC and T>MIC.

The table below shows how different antimicrobials are categorised based on PK/PD parameters.

If you require a screen reader-compatible version this is available as a PDF.

Why is all this important?

Optimising dosing (the dose itself and dosing schedule) according to PK/PD parameters will maximise bacterial killing and will be particularly important for those with or who are at risk of severe infection e.g. those with impaired immunity. Several factors need to be considered when approaching optimising PK/PD for individual circumstances:

• The organism: The MIC (organisms with high MICs to an antimicrobial may be interpreted as resistant, as standard doses would not be effective enough to treat an infection) and the likelihood of developing resistance.
• The site of infection: This is an important factor in how effective an antimicrobial is; infected sites that are difficult to penetrate, e.g., abscesses, or anatomically distinct sites such as the cerebral spinal fluid (CSF), will be more difficult to treat and may require higher or more frequent dosing of antimicrobials.
• The antimicrobial: Its Vd as determined by whether it is water—or lipid-soluble and its interactions with other medications, which may affect its antibacterial effect.
• The patient: Renal function, hepatic function, albumin levels and differences in physiological states such as in pregnancy and in neonates. Some of these patient factors will be considered later in the course.

Click next to move on to the next step, where we will begin to examine the pharmacokinetics of aminoglycosides more specifically.