JAC Advance Access published online on October 7, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh443
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
* To whom correspondence should be addressed. E-mail: christian.joukhadar{at}meduniwien.ac.at.
Objectives: Plasma protein binding (PPB) is known to impair the antimicrobial activity of Methods: Bacterial time-killing curves were employed in the absence and presence of physiological albumin concentrations (40 g/L). Moxifloxacin, ampicillin and oxacillin were investigated. Fosfomycin, a non-protein bound antibiotic was used for comparison. Simulations were carried out by employing concentrations of antibiotics of one-fourth of the minimal inhibitory concentration (MIC), equal to the MIC and four-fold the MIC of one select bacterial strain (Staphylococcus aureus ATCC 29213). To correlate bacterial killing to the extent of PPB, bacterial time-killing curves were plotted using the calculated free and the total drug concentration. Results: Bacterial killing by fosfomycin was not affected by the addition of albumin. The antimicrobial activity of oxacillin and ampicillin was reduced in the presence of albumin as expected by the calculation of the free fraction of these antibiotics. Adding albumin to moxifloxacin resulted in a significant decrease in bacterial killing of more than 1 log10 cfu/mL after a period of 8 h when the moxifloxacin concentration was equal to the respective MIC. Conclusions: Our data confirm the view that albumin substantially impairs the antimicrobial activity of antibiotics including moxifloxacin, a member of the class of fluoroquinolones.
Revised August 26, 2004
Accepted September 2, 2004
Original article
Impact of plasma protein binding on antimicrobial activity using time-killing curves
2 Department of Internal Medicine I, Division of Infectious Diseases and Chemotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
3 Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Institute of Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
Abstract 
-lactams, but its impact on the activity of other classes of antimicrobials such as fluoroquinolones is controversial. This study was undertaken to investigate the effect of PPB on bacterial killing by selected antibiotics and moxifloxacin, which served as a model compound for the class of fluoroquinolones.
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