Journal of Antimicrobial Chemotherapy, Vol 42, 179-187, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
KS Thomson and CC Sanders
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.
ORIGINAL ARTICLES
The effects of increasing levels of quinolone resistance on in-vitro activity of four quinolones
Center for Research in Anti-Infectives & Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NB 68178, USA.
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