uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mutant prevention concentrations of ciprofloxacin for urinary tract infection isolates of Escherichia coli
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Show others and affiliations
2005 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 55, no 6, 938-943 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To measure the mutant prevention concentration (MPC) of ciprofloxacin for a set of urinary tract infection (UTI) Escherichia coli isolates with different levels of susceptibility and determine whether MPC can be predicted from MIC.

Methods: MPC was defined as the lowest ciprofloxacin concentration that prevented the growth of resistant colonies when 1010 bacteria were spread on solid medium and incubated for 96 h at 37°C. MIC was measured by Etest. Bacteria surviving (persisting) at MPC were isolated and quantified from agar plugs taken after 96 h. The genes hipA and hipB were amplified by PCR from persisters and sequenced.

Results: Isolates with MICs above the NCCLS breakpoint for ciprofloxacin resistance (4 mg/L) typically have MPCs greater than 32 mg/L. Isolates with MICs below the breakpoint for ciprofloxacin susceptibility (1 mg/L) have MPCs up to 5 mg/L. MPC/MIC is ∼16 for most susceptible isolates but there are several notable exceptions (MPC/MIC > 100). Resistant colonies arising one dilution step below MPC often had MIC > MPC. In every case tested, a proportion of cells survived (persisted), but did not grow into colonies, at MPC, without any increase in MIC.

Conclusions: MPCs were determined for all ciprofloxacin-susceptible isolates. MPC is not accurately predicted from MIC. Colonies selected below MPC frequently have MIC > MPC, suggesting multiple mutations. A small fraction of cells from all strains tested survived for 96 h at MPC, without any associated increase in MIC. These survivors/persisters are not hipAB mutants.

Place, publisher, year, edition, pages
2005. Vol. 55, no 6, 938-943 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95000DOI: 10.1093/jac/dki136OAI: oai:DiVA.org:uu-95000DiVA: diva2:169046
Available from: 2006-10-20 Created: 2006-10-20 Last updated: 2011-07-18Bibliographically approved
In thesis
1. Relation Between Drug Exposure and Selection of Antibiotic Resistant Bacteria
Open this publication in new window or tab >>Relation Between Drug Exposure and Selection of Antibiotic Resistant Bacteria
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The worldwide increase in antibiotic resistance is a concern for public health. When the appropriate antibiotic dosage is determined, the priorities are efficacy and toxicity. The aim of this thesis was to gain knowledge about the most efficient dosing regimens in order to minimize the emergence and selection of antibiotic-resistant mutants. We also wanted to assess the impact of antibiotic selective pressure and host to host transmission for the dissemination of resistance.

Escherichia coli bacteria with different levels of cefotaxime susceptibility were competed in an in vitro kinetic model, demonstrating a complex selection of low-level resistance influenced e.g. by the time duration of selective concentrations and the rise of new mutants. We also constructed a mathematical model incorporating biologically relevant parameters and showed its usefulness when assessing the risks of resistance development.

When E. coli populations with pre-existing fluoroquinolone-resistant mutants were exposed to simulated serum concentrations, several currently used doses of fluoroquinolones clearly enhanced the development and selection of resistance.

The mutant prevention concentration (MPC) was measured for several E. coli isolates with different fluoroquinolone susceptibilities, and because of fluctuating antibiotic concentrations in the human body, the pharmacokinetics was considered when evaluating MPC. Results indicate that the area under the serum concentration time curve in relation to the MPC may be a useful predictor for emergence of resistance.

In the commensal flora of healthy human couples we noted a high frequency of trimethoprim-resistant E. coli. There was also an extensive sharing and transmission of E. coli clones. Treating the female with trimethoprim reduced the number of intestinal E. coli which might have facilitated the transmission from the male partner. These findings suggest that the rate of transmission is high and effectively contributes to the spread of both susceptible and antibiotic-resistant E. coli in intrafamilial settings.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 184
Keyword
Microbiology, Pharmacokinetics, Pharmacodynamics, Antibiotic resistance, Selection, Transmission, Mathematical model, Escherichia coli, Mikrobiologi
Identifiers
urn:nbn:se:uu:diva-7197 (URN)91-554-6685-0 (ISBN)
Public defence
2006-11-10, Hörsalen, Klinisk Bakteriologi, Akademiska Sjukhuset ing D1, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-10-20 Created: 2006-10-20 Last updated: 2011-07-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Hughes, Diarmaid

Search in DiVA

By author/editor
Hughes, Diarmaid
By organisation
Department of Cell and Molecular BiologyClinical Bacteriology
In the same journal
Journal of Antimicrobial Chemotherapy
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 821 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf