title: Activity of gatifloxacin against strains resistant to ofloxacin and ciprofloxacin and its ability to select for less susceptible bacterial variants.
abstract: Gatifloxacin is an 8-methoxy fluoroquinolone. On quinolones, this side chain imparts increased activity against Gram-positive bacteria and enhanced killing. Gatifloxacin was tested against ofloxacin non-susceptible (ofloxacin MIC>2 mg/l) strains of Streptococcus pneumoniae (gatifloxacin MIC(90), 1 mg/l) and methicillin-resistant Staphylococcus aureus (MRSA, gatifloxacin MIC(90), 4 mg/l), and to ciprofloxacin non-susceptible (ciprofloxacin MIC>1 mg/l) strains of Escherichia coli (gatifloxacin MIC(90),>16 mg/l) and ciprofloxacin non-susceptible (ciprofloxacin MIC>0.06 mg/l) Neisseria gonorrhoeae (gatifloxacin MIC(50), 0.12 mg/l and MIC(90), 0.5 mg/l). Though gatifloxacin showed some reduced susceptibility to these populations, the MIC(50) and MIC(90) values suggest that gatifloxacin may be useful against pneumococci and some gonococcal strains not susceptible to other fluoroquinolones. Gatifloxacin did not select for less susceptible variants of MRSA and pneumococci, in contrast to the 10- to 100-fold higher selection frequencies with ciprofloxacin and ofloxacin. The single-step E. coli mutants selected by gatifloxacin and the comparator quinolones had quinolone MICs within the susceptible range. These data suggest that gatifloxacin use may hinder the development of quinolone-resistance, particularly in Gram-positive bacteria.
authors.affiliation: Department of Microbiology, Bristol-Myers Squibb Company, 5 Research Parkway, 06492, Wallingford, CT, USA. fungtomj@bms.com
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
authors.forename: E
authors.initials: E
authors.lastname: Gradelski
authors.forename: E
authors.initials: E
authors.lastname: Huczko
authors.forename: B
authors.initials: B
authors.lastname: Minassian
authors.forename: D P
authors.initials: DP
authors.lastname: Bonner
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics; D015242:Ofloxacin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin