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Antimicrobial Agents and Chemotherapy, May 1999, p. 1013-1019, Vol. 43, No. 5
Department of Pharmacology, School of
Medicine, University of Milan, Milan, Italy
Received 22 December 1997/Returned for modification 6 January
1999/Accepted 14 February 1999
It has been reported that subinhibitory concentrations (sub-MICs)
of some fluoroquinolones are still capable of affecting the topological
characteristics of DNA (inhibition DNA-gyrase) and that this leads to a
reduction in some of the factors responsible for bacterial virulence
(by means of the disruption of protein synthesis and alterations in
phenotype expression), even though the microorganisms themselves are
not killed. The present study investigated the ability of sub-MICs of
rufloxacin, an orally absorbed monofluorinated quinolone with a long
half-life (28 to 30 h), to interfere with the bacterial virulence
parameters of adhesiveness, hemagglutination, hydrophobicity, motility,
and filamentation, as well as their interactions with host neutrophilic defenses such as phagocytosis, killing, and oxidative bursts. It was
observed that Escherichia coli adhesiveness was
significantly reduced at rufloxacin concentrations of 1/32 MIC,
hemagglutination and hydrophobicity were significantly reduced at
concentrations of, respectively, 1/4 MIC and 1/8 MIC, and motility was
significantly reduced at concentrations of 1/16 MIC; filamentation was
still present at concentrations of 1/4 MIC. Phagocytosis was not
affected, but killing significantly increased from 1/2 MIC to 1/8 MIC;
oxidative bursts measured by means of chemiluminescence were not
affected. The fact that sub-MICs are still effective in interfering
with the parameters of bacterial virulence is useful information that needs to be correlated with pharmacokinetic data in order to extend our
knowledge of the most effective concentrations that can be used to
optimize treatment schedules, for example, single administrations, particularly in noncomplicated lower urinary tract infections.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Pharmacodynamic Effects of Subinhibitory
Concentrations of Rufloxacin on Bacterial Virulence
Factors
*
Corresponding author. Mailing address: Dept. of
Pharmacology, Via Vanvitelli 32, 20129 Milano, Italy. Phone:
39-2-70146363. Fax: 39-2-70146371. E-mail: bragapc{at}unimi.it.
Antimicrobial Agents and Chemotherapy, May 1999, p. 1013-1019, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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