Document Detail


In vitro activities of garenoxacin (BMS-284756) against Haemophilus influenzae isolates with different fluoroquinolone susceptibilities.
MedLine Citation:
PMID:  14576114     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The in vitro activity of garenoxacin (BMS-284756) against 62 clinical Haemophilus influenzae isolates with different fluoroquinolone susceptibilities was determined by the microdilution susceptibility testing method and compared with the activities of other oral quinolones and nonquinolone oral antimicrobial agents. Cefixime presented the highest intrinsic activity (MIC at which 50% of the isolates tested were inhibited [MIC(50)], 0.01 microg/ml), followed by garenoxacin, moxifloxacin, and ciprofloxacin (MIC(50), 0.06 microg/ml), levofloxacin (MIC(50), 0.12 microg/ml), cefuroxime (MIC(50), 1.0 microg/ml), and amoxicillin-clavulanate (MIC(50), 1.0/0.5 microg/ml), amoxicillin (MIC(50), 2 microg/ml), azithromycin (MIC(50), 4 microg/ml), and erythromycin (MIC(50), 8 microg/ml). In strains with ciprofloxacin MICs of < or =0.06 microg/ml, ciprofloxacin and garenoxacin displayed similar MIC(50)s and MIC(90)s, one dilution lower than those of moxifloxacin and levofloxacin. For strains for which ciprofloxacin MICs were > or = 0.12 microg/ml, MIC(50)s were similar for the four quinolones tested, although garenoxacin presented the widest activity range (0.03 to 32 microg/ml) and the highest MIC at which 90% of the isolates tested were inhibited (16.0 microg/ml). For strains without amino acid changes in the quinolone resistance determining region (QRDR) of GyrA and ParC, garenoxacin MICs were < or =0.03 microg/ml; with a single amino acid change in GyrA, garenoxacin MICs were 0.06 to 0.12 microg/ml; with one amino acid change each in GyrA and ParC, garenoxacin MICs were 0.5 to 2.0 micro g/ml; one amino acid change in ParC combined with two amino acid changes in GyrA increased the MICs to > or = 4 microg/ml for all assayed quinolones. We conclude that garenoxacin has excellent activity against H. influenzae, although progressive acquired resistance was observed by step-by-step mutation in the QRDR of gyrA and parC.
Authors:
María Pérez-Vázquez; Federico Román; Belen Aracil; Rafael Cantón; José Campos
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  47     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-24     Completed Date:  2004-07-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3539-41     Citation Subset:  IM    
Affiliation:
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda-Madird, Spain.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Anti-Infective Agents / pharmacology*
DNA Gyrase / genetics
DNA Topoisomerase IV / genetics
Fluoroquinolones / pharmacology*
Haemophilus Infections / microbiology
Haemophilus influenzae / drug effects*
Humans
Microbial Sensitivity Tests
Mutation / genetics
Quinolones / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Fluoroquinolones; 0/Quinolones; 0/garenoxacin; EC 5.99.1.-/DNA Gyrase; EC 5.99.1.-/DNA Topoisomerase IV
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