Table IV.

Advantages and Limitations of the MIC and the TKC approach

	Advantages	Limitations	References
MIC	Easy to perform	Static approach, which does not account for dynamic pharmacokinetics	61,72
	Currently the most widely used pharmacodynamic parameter for pharmacokinetic/pharmacodynamic modeling of antibiotic	Implies subjective assessment of turbidity changes
	MBC can be determined	Only twofold dilution steps, small changes might be overseen
	Permits easy analyzing of effects of drug combinations on bacterial growth	No information on “killing-kinetics”
		For visible growth colony forming units per milliliter of 107 necessary, i.e., less pronounced growth is overseen
TKC	Microbial killing and growth is observed as a function of both time at a given antibiotic concentration, i.e., “killing-kinetics” is depicted	Elaborate technique	48,72,73
	Curves in the presence (kill curves) and absence (growth curves) of antibiotic can be compared	Commonly only static approach, which does not account for dynamic pharmacokinetics
	Antibiotic concentrations can either be held constant or changed to mimic an in vivo concentration profile
	Exact determination of colony forming units per milliliter

The MIC is obtained by making twofold dilutions of the test antibiotic in a liquid culture medium, inoculating it with 5 × 10⁵ cfu/mL of bacteria, and incubating it at 35–37°C for 18–24 h. The smallest amount of antibiotic that inhibits visible growth of the microorganism represents the MIC. The TKC is obtained by plotting bacterial growth against time in the presence of chosen antibiotic concentrations. Bacterial counts are obtained as by predefined time points, samples are removed from the culture tubes, serially diluted, and plated onto agar plates, which are incubated for 24 h at 37°C. The colonies are then counted and backextrapolated to the original volume to determine colony forming units per milliliter

MIC Minimal inhibitory concentration, TKC Time Kill Curve