Evaluation of once-daily vancomycin against methicillin-resistant Staphylococcus aureus in a hollow-fiber infection model

Anthony M Nicasio, Jurgen Bernd Bulitta, Thomas P Lodise Jr., Rebecca E D'Hondt, Robert Kulawy, Arnold Louie, George L Drusano

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27 Citations (Scopus)

Abstract

For methicillin-resistant Staphylococcus aureus (MRSA) infections, data suggest that the clinical response is significantly better if the total vancomycin area under the concentration-time curve (AUC)/MIC ratio is =400. While the AUC/MIC ratio is the accepted pharmacokinetic/pharmacodynamic (PK/PD) index for vancomycin, this target has been achieved using multiple daily doses. We are unaware of a systematically designed dose fractionation study to compare the bactericidal activity of once-daily administration to that of traditional twice-daily administration. A dose fractionation study was performed with vancomycin in an in vitro hollow-fiber infection model against an MRSA USA300 strain (MIC of 0.75 ?g/ml) using an inoculum of 10 6CFU/ml. The three vancomycin regimens evaluated for 168 h were 2 g every 24 h (q24h) as a 1-h infusion, 1 g q12h as a 1-h infusion, and 2 g q24h as a continuous infusion. Free steady-state concentrations (assuming 45 binding) for a total daily AUC/MIC ratio of =400 were simulated for all regimens. A validated liquid chromatography-tandem mass spectrometry method was used to determine vancomycin concentrations. Although once-daily and twice-daily dosage regimens exhibited total trough concentrations of
Original languageEnglish
Pages (from-to)682 - 686
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume56
Issue number2
DOIs
Publication statusPublished - 2012

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