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J Antimicrob Chemother ; 65(12): 2530-3, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20940181

ABSTRACT

OBJECTIVES: Finafloxacin is an investigational fluoroquinolone exhibiting broad-spectrum activity that is enhanced under slightly acidic conditions (pH 5.0-6.5). The impact of individual and combinations of chromosomal mutations (gyrA, parC and marR) and the plasmid-mediated fluoroquinolone resistance mechanisms QepA1, QnrA1, QnrB1, QnrS1 and AAC(6')-Ib-cr were investigated. METHODS: The MICs of finafloxacin, compared with those of ciprofloxacin, levofloxacin and moxifloxacin, were determined at pH 5.8 and 7.2. RESULTS: MICs of finafloxacin compared with other fluoroquinolones at pH 5.8 were lower by a factor of 2-256. MICs of finafloxacin were unaffected by QepA1. Moreover, finafloxacin appeared not to be a substrate for AAC(6')-Ib-cr. CONCLUSIONS: Compared with ciprofloxacin, levofloxacin and moxifloxacin, finafloxacin shows higher activity especially at pH 5.8 against Escherichia coli mutants expressing known fluoroquinolone resistance determinants alone and in combinations.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Bacterial/genetics , Escherichia coli/drug effects , Fluoroquinolones/pharmacology , Plasmids/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Chromosomes, Bacterial/genetics , DNA Gyrase/chemistry , DNA Gyrase/genetics , DNA Gyrase/metabolism , DNA Topoisomerase IV/chemistry , DNA Topoisomerase IV/genetics , DNA Topoisomerase IV/metabolism , DNA, Bacterial/genetics , Escherichia coli/genetics , Humans , Hydrogen-Ion Concentration , Microbial Sensitivity Tests
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