Skip Navigation



JAC Advance Access published online on September 19, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl361
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
58/5/1054    most recent
dkl361v1
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 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 Cattoir, V.
Right arrow Articles by Cambau, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cattoir, V.
Right arrow Articles by Cambau, E.
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
Received May 26, 2006
Revised July 25, 2006
Accepted August 10, 2006

Brief report

In vivo selection during ofloxacin therapy of Escherichia coli with combined topoisomerase mutations that confer high resistance to ofloxacin but susceptibility to nalidixic acid

Vincent Cattoir 1, Philippe Lesprit 2, Christine Lascols 1, Erik Denamur 3, Patrick Legrand 1, Claude-James Soussy 1, and Emmanuelle Cambau 1 *

1 Service de Bactériologie-Virologie-Hygiène, AP-HP CHU Henri Mondor, Université Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France
2 Unité de Contrôle Épidémiologique et Prévention de l'Infection, AP-HP CHU Henri Mondor, Créteil, France
3 Inserm U722 and University Paris 7 Denis Diderot, Site Xavier Bichat, France

* To whom correspondence should be addressed.
Emmanuelle Cambau, E-mail: emmanuelle.cambau{at}hmn.aphp.fr


  Abstract

Objectives: To investigate quinolone resistance mechanisms in an Escherichia coli clinical isolate (Ar2) resistant to ofloxacin but susceptible to nalidixic acid selected after 10 days of ofloxacin therapy in a patient with prostatitis.

Methods: Molecular typing (ERIC-PCR and RAPD), antibiotic susceptibility and gyrA, gyrB, parC and parE QRDR sequences were compared for E. coli Ar2 and a wild-type E. coli (Ar1) isolated 2 months earlier in the same patient. Ofloxacin-resistant mutants were selected in vitro in order to reproduce the mutations observed and the original phenotype.

Results: The two strains were similar with regard to antibiotic susceptibility except quinolones and for ERIC-PCR and RAPD patterns, suggesting a clonal relationship and acquisition of quinolone resistance by chromosomal mutation. Quinolone MICs were 3, 0.12, 0.05 and 0.02 mg/L of nalidixic acid, ofloxacin, levofloxacin and ciprofloxacin, respectively, for E. coli Ar1 and 6, 32, 8 and 1 mg/L, respectively, for E. coli Ar2. The strain Ar2 harboured two substitutions, Gly-81->Asp in GyrA and Ser-80->Arg in ParC. Introduction into E. coli Ar2 of the wild-type gyrA fully complemented fluoroquinolone resistance. Although the strain was not a hypermutator, ofloxacin first-step resistant mutants with gyrA mutations were easily obtained from E. coli Ar1 and 25% of them were at codon 81. In vitro stepwise combination of Gly-81->Asp in GyrA and Ser-80->Arg in ParC reproduced the original phenotype in E. coli KL16.

Conclusions: A double topoisomerase mutant was selected in vivo by 10 days ofloxacin. The mutations were originally combined for a result of ofloxacin resistance but nalidixic acid susceptibility.

Keywords: fluoroquinolones; parC; DNA gyrase A; QRDRs; gyrA; prostatitis.
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
I. Almahmoud, E. Kay, D. Schneider, and M. Maurin
Mutational paths towards increased fluoroquinolone resistance in Legionella pneumophila
J. Antimicrob. Chemother., August 1, 2009; 64(2): 284 - 293.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
E. Cambau, S. Matrat, X.-S. Pan, R. Roth Dit Bettoni, C. Corbel, A. Aubry, C. Lascols, J.-Y. Driot, and L. M. Fisher
Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli
J. Antimicrob. Chemother., March 1, 2009; 63(3): 443 - 450.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
V. Cattoir, L. Poirel, and P. Nordmann
Plasmid-Mediated Quinolone Resistance Pump QepA2 in an Escherichia coli Isolate from France
Antimicrob. Agents Chemother., October 1, 2008; 52(10): 3801 - 3804.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
V. Cattoir, P. Nordmann, J. Silva-Sanchez, P. Espinal, and L. Poirel
ISEcp1-Mediated Transposition of qnrB-Like Gene in Escherichia coli
Antimicrob. Agents Chemother., August 1, 2008; 52(8): 2929 - 2932.
[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.