Skip Navigation


JAC Advance Access originally published online on November 13, 2006
Journal of Antimicrobial Chemotherapy 2007 59(2):254-263; doi:10.1093/jac/dkl469
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
59/2/254    most recent
dkl469v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wiuff, C.
Right arrow Articles by Andersson, D. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiuff, C.
Right arrow Articles by Andersson, D. I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Antibiotic treatment in vitro of phenotypically tolerant bacterial populations

Camilla Wiuff* and Dan I. Andersson

Department of Medical Biochemistry and Microbiology, Uppsala University Box 582, S-751 23 Uppsala, Sweden

Received 2 August 2006; returned 4 October 2006; revised 19 October 2006; accepted 21 October 2006

*Correspondence address. Health Protection Scotland, Section for HAI & IC, 1 Cadogan Square, Cadogan Street, Glasgow G2 7HF, UK. Tel: +44-141-2822927; Fax: +44-141-8470399; E-mail: camilla.wiuff{at}hps.scot.nhs.uk

Objectives: Most pharmacodynamic models used for design of treatment regimens are based on time–kill data obtained with normal cells in the susceptible state without taking into account the killing kinetics of the antibiotic-tolerant cells in the population. We compared the microbiological efficacy of six antibiotics against tolerant cells and by mathematical modelling explored the potential clinical implications of tolerance.

Methods: Tolerant cells were obtained by filtration of bacterial cultures of Escherichia coli MG1655 after antibiotic exposure. Killing kinetics of the tolerant cells was compared with that of exponentially growing naive cells. To examine the nutrient dependency of the reversion from the tolerant state to the susceptible state, tolerant cells were re-suspended in Luria–Bertani and PBS and re-exposed to antibiotics. A mathematical model was used to explore the clinical implications of antibiotic tolerance.

Results: Streptomycin was the most efficient drug against tolerant cells. Ciprofloxacin and ampicillin had intermediate activity against tolerant cells while rifampicin, tetracycline and erythromycin had poor activity against tolerant cells. No correlation could be established between the microbiological efficacies against susceptible and tolerant cells. Reversion from tolerance to susceptibility was dependent on the presence of nutrients and growth. Computer simulations demonstrated that the efficacy of antibiotics against tolerant cell populations has a large influence on treatment outcome.

Conclusions: The in vitro killing kinetics of tolerant cells is antibiotic-dependent and different from that of cells in the susceptible state. This difference in efficacy could have an influence on treatment outcome and tolerance should therefore be studied further in vivo.

Keywords: antibiotic tolerance , persistence , treatment regimens , killing kinetics , pharmacodynamic models


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
K. I. Udekwu, N. Parrish, P. Ankomah, F. Baquero, and B. R. Levin
Functional relationship between bacterial cell density and the efficacy of antibiotics
J. Antimicrob. Chemother., April 1, 2009; 63(4): 745 - 757.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.