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Author Notes:

Correspondence: E-mail: klas.udekwu@ki.se

Conceived and designed the experiments: KU BRL.

Performed the experiments: KU.

Analyzed the data: KU BRL.

Contributed reagents/materials/analysis tools: KU BRL.

Wrote the paper: KU BRL.

Performed simulations: BRL.

The authors have declared that no competing interests exist.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

This work was supported by a grant from the United States National Institutes of Health (GM091875 to BRL).

Keywords:

  • Antibiotics
  • Continuous cultures
  • Bacterial biofilms
  • Staphylococcus aureus
  • Population density
  • Vancomycin
  • Drug therapy
  • Plankton

Staphylococcus aureus in Continuous Culture: A Tool for the Rational Design of Antibiotic Treatment Protocols

Journal Title:

PLoS ONE

Volume:

Volume 7, Number 7

Publisher:

, Pages e38866-e38866

Type of Work:

Article | Final Publisher PDF

Abstract:

In vitro measures of the pharmacodynamics of antibiotics that account for the factors anticipated for bacteria in infected patients are central to the rational design of antibiotic treatment protocols. We consider whether or not continuous culture devices are a way to obtain these measures. Staphylococcus aureus PS80 in high-density continuous cultures were exposed to oxacillin, ciprofloxacin, vancomycin, gentamicin, daptomycin and linezolid. Contrary to results from low density retentostats as well as to predictions of traditional PK/MIC ratios, daily dosing with up to 100× MIC did not clear these cultures. The densities of S. aureus in these cultures oscillated with constant amplitude and never fell below 105 CFU per ml. Save for daptomycin “treated” populations, the densities of bacteria in these cultures remained significantly below that of similar antibiotic-free cultures. Although these antibiotics varied in their pharmacodynamic properties there were only modest differences in their mean densities. Mathematical models and experiments suggest that the dominant factor preventing clearance was wall-adhering subpopulations reseeding the planktonic population which can be estimated and corrected for. Continuous cultures provide a way to evaluate the potential efficacy of antibiotic treatment regimes in vitro under conditions that are more clinically realistic and comprehensive than traditional in vitro PK/PD indices.

Copyright information:

Copyright 2012 Udekwu, Levin.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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