To predict the effects of combined use of antibiotics on their pharmacodynamics, the susceptibility of Staphylococcus aureus to linezolid–rifampicin combinations was tested at concentration ratios equal to the ratios of 24-area under the concentration–time curve (AUC24) simulated in an in vitro dynamic model. The linezolid MICs in combination with rifampicin decreased 8- to 67-fold. The rifampicin MICs were similar with or without linezolid. The enhanced activity of linezolid combined with rifampicin increased the AUC24/MIC ratios and provided more pronounced antibacterial effects compared with single treatments. The areas between the control growth and time-kill curves (ABBCs) determined in combined and single treatments with linezolid were plotted against AUC24/MIC on the same graph (r2 0.94). These findings suggest that the effects of linezolid–rifampicin combinations can be predicted by AUC24/MICs of linezolid using its MIC determined at pharmacokinetically derived linezolid-to-rifampicin concentration ratios.
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Golikova et al. (2017) studied this question.
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