title: The effects of increasing levels of quinolone resistance on in-vitro activity of four quinolones.
abstract: A panel of 266 clinically isolated Gram-positive cocci and Gram-negative bacilli with varying levels of resistance to ciprofloxacin were analysed for susceptibility to Du-6859a, ciprofloxacin, ofloxacin, temafloxacin and nalidixic acid. Staphylococci were divided into ciprofloxacin-susceptible, moderately resistant and highly resistant subgroups. Du-6859a was the most potent quinolone against all taxa. As ciprofloxacin resistance increased to high levels, MICs of all quinolones increased but Du-6859a MICs increased least, and ciprofloxacin MICs increased most. Less susceptible single-step mutants were selected from 80% of 15 representative clinical isolates exposed to ciprofloxacin, 71% of isolates exposed to temafloxacin, 67% of isolates exposed to Du-6859a and 53% of isolates exposed to ofloxacin. Du-6859a inhibited more mutants (67%) at a concentration of 1 mg/L than did the other quinolones (26-43%) at their susceptible breakpoints. Du-6859a was the most rapidly bactericidal quinolone in time-kill studies with Enterococcus faecalis and Enterococcus faecium. This study indicated that Du-6859a is more potent than the comparator quinolones, is less affected by the mechanisms responsible for high-level quinolone resistance and may be less likely to select resistant mutants if it has a susceptible breakpoint of 1 mg/L.
authors.affiliation: Center for Research in Anti-Infectives & Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NB 68178, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Thomson
authors.forename: C C
authors.initials: CC
authors.lastname: Sanders
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C054745:temafloxacin; D009268:Nalidixic Acid; D002939:Ciprofloxacin; C076246:sitafloxacin; D015242:Ofloxacin