Effect of Low-Level Resistance on Subsequent Enrichment of Fluoroquinolone-Resistant Streptococcus pneumoniae in Rabbits

Background. We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window. Methods. Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentra...

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Bibliographic Details
Published in:The Journal of infectious diseases 2004-10, Vol.190 (8), p.1472-1475
Main Authors: Etienne, Manuel, Croisier, Delphine, Charles, Pierre-Emmanuel, Lequeu, Catherine, Piroth, Lionel, Portier, Henri, Drlica, Karl, Chavanet, Pascal
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacology
Anti-Infective Agents - therapeutic use
Antibacterials
Antimicrobials
Aza Compounds - therapeutic use
Bacteria
Bacteriology
Biological and medical sciences
Ciprofloxacin - therapeutic use
DNA Topoisomerase IV - genetics
Dosage
Drug Resistance, Bacterial - drug effects
Drug Resistance, Bacterial - genetics
Fluoroquinolones
Fluoroquinolones - pharmacology
Fundamental and applied biological sciences. Psychology
Genetic mutation
Infectious diseases
Lung - microbiology
Medical sciences
Microbiology
Miscellaneous
Mutation
Pharmacokinetics
Pneumococcal Infections - drug therapy
Pneumococcal Infections - microbiology
Pneumococcal pneumonia
Quinolines - therapeutic use
Quinolones
Rabbits
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - isolation & purification
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Summary:Background. We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window. Methods. Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility. Results. Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not. However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined. Conclusions. A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements.
ISSN:0022-1899
1537-6613
DOI:10.1086/423853