Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.

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. Staphylo...

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Main Authors: Klas I Udekwu, Bruce R Levin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3401188?pdf=render
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author Klas I Udekwu
Bruce R Levin
author_facet Klas I Udekwu
Bruce R Levin
author_sort Klas I Udekwu
collection DOAJ
description 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 10(5) 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.
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spelling doaj.art-9bc4a043b18c456d901ee6460400a42e2022-12-21T18:23:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e3886610.1371/journal.pone.0038866Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.Klas I UdekwuBruce R LevinIn 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 10(5) 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.http://europepmc.org/articles/PMC3401188?pdf=render
spellingShingle Klas I Udekwu
Bruce R Levin
Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
PLoS ONE
title Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
title_full Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
title_fullStr Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
title_full_unstemmed Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
title_short Staphylococcus aureus in continuous culture: a tool for the rational design of antibiotic treatment protocols.
title_sort staphylococcus aureus in continuous culture a tool for the rational design of antibiotic treatment protocols
url http://europepmc.org/articles/PMC3401188?pdf=render
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AT brucerlevin staphylococcusaureusincontinuouscultureatoolfortherationaldesignofantibiotictreatmentprotocols