Pharmacodynamic effects of subinhibitory concentrations of rufloxacin on bacterial virulence factors.
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.
Braga
P C
PC
Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy. bragapc@unimi.it
Sala
M T
MT
Dal Sasso
M
M
D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001422:Bacterial Adhesion / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D024841:Fluoroquinolones; D006801:Humans; D009504:Neutrophils / Q000382:microbiology*; D010587:Phagocytosis / Q000187:drug effects; D015363:Quinolones / Q000493:pharmacokinetics*; D016897:Respiratory Burst / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C060328:rufloxacin