JAC Advance Access published online on December 19, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh036
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Institute for Medical Microbiology and Hygiene, University
of Regensburg, Regensburg, Germany
* Corresponding author. E-mail: Hans-Joerg.Linde{at}klinik.uni-regensburg.de.
Received 4 August 2003
; revised 10 October 2003
; accepted 23 October 2003
Objectives: We used two different
strains of Escherichia coli, E.coli ATCC 25922
and a recent urinary isolate from a clinical sample, to investigate in vitro how the MIC and mutant prevention concentration
(MPC) are affected by different temperatures (37 or 20°C)
or oxygen tension (aerobic or anaerobic atmosphere; MIC, MICan;
MPC, MPCan). Materials and methods: MIC and MPC for E.coli ATCC
25922 and the clinical isolate were determined on agar containing
ciprofloxacin or levofloxacin, and for the ATCC strain on agar supplemented
with nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin
or clinafloxacin. Results: Results for the ATCC strain and the
clinical strain for ciprofloxacin or levofloxacin were similar.
The MPC values for E.coli ATCC 25922 were 2 x MIC (trovafloxacin), 4 x MIC
(ciprofloxacin, norfloxacin, ofloxacin), 8 x MIC
(clinafloxacin, levofloxacin), 16 x MIC
(sparfloxacin) and 32 x MIC (nalidixic
acid) at 37°C and under aerobic conditions.
Generally, a 37°C aerobic atmosphere
was associated with the highest MPC values. As an exception, both
the MIC and the MPC of ciprofloxacin were higher under anaerobic
versus aerobic conditions (MICan Conclusions: As calculated from our model in
respect to the length of the selection period, long serum half-lives
of recently developed compounds could not be compensated for by
a more favourable activity in terms of MPC. Higher concentrations
of ciprofloxacin may be required under an anaerobic atmosphere to
prevent the emergence of resistant mutants among 1010 cfu.
Keywords: MPC, quinolones, resistance
Mutant prevention concentration of nalidixic acid,
ciprofloxacin, clinafloxacin, levofloxacin, norfloxacin, ofloxacin,
sparfloxacin or trovafloxacin for Escherichia coli under
different growth conditions
8 x MIC; MPCan = 4 x MPC) for both E.coli isolates.
Irrespective of the quinolone or growth conditions, the MIC for
mutants was 1-256 x wild-type
MIC. Calculated from published serum half-lives and the MPC values
from this study, a putative selection period, in which resistant
mutants might be selected, was calculated to be 14 h for nalidixic
acid, 16 h for norfloxacin and ciprofloxacin, 28 h for ofloxacin, 30
h for trovafloxacin, 35 h for levofloxacin, 40 h for clinafloxacin,
and 120 h for sparfloxacin.
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