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Predicting effects of antibiotic combinations using MICs determined at pharmacokinetically derived concentration ratios: in vitro model studies with linezolid- and rifampicin-exposed Staphylococcus aureus.

Authors
  • Golikova, Maria V1
  • Strukova, Elena N1
  • Portnoy, Yury A1
  • Dovzhenko, Svetlana A1
  • Kobrin, Mikhail B1
  • Zinner, Stephen H2
  • Firsov, Alexander A1
  • 1 a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • 2 b Department of Medicine , Mount Auburn Hospital, Harvard Medical School , Cambridge , MA , USA.
Type
Published Article
Journal
Journal of chemotherapy (Florence, Italy)
Publication Date
Oct 01, 2017
Volume
29
Issue
5
Pages
267–273
Identifiers
DOI: 10.1080/1120009X.2017.1281093
PMID: 28192070
Source
Medline
Keywords
License
Unknown

Abstract

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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