Journal of Antimicrobial Chemotherapy (2000) 45, 15-25
© 2000 The British Society for Antimicrobial Chemotherapy
Sub-MIC concentrations of cefodizime interfere with various factors affecting bacterial virulence
Department of Pharmacology, School of Medicine, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
The molecular array of the outermost surface of bacteria and their physico-chemical characteristics modulate various functions which, when expressed in terms of the human environment, are generally known as factors of bacterial virulence. The present study investigated the ability of sub-MIC concentrations of cefodizime to interfere with the virulence factors of Escherichia coli. Bacterial adhesiveness to human epithelial cells was inhibited down to 1/32 x MIC of cefodizime, an antibiotic that is also capable of inducing the widespread production of filamentous forms at levels ranging from 1/2 to 1/8 x MIC. Given that this interfered with the correct evaluation of other virulence parameters, the study was extended to consider the effects of 1/16 to 1/128 x MIC. Sub-MIC concentrations of cefodizime inhibit haemagglutination, hydrophobicity and electrophoretic mobility, which are correlated with each other and provide clues relating to the physico-chemical characteristics of the outer surface. Cefodizime also reduces swarming. Phagocytosis was not affected but killing increased significantly. Oxidative bursts investigated by a chemiluminescence procedure were not modified. The interpolation of these pharmacodynamic findings with pharmacokinetic curves indicates that the effect of sub-MIC concentrations of cefodizime can prolong antimicrobial effects on virulence determinants up to 12 h after the antibiotic concentration has fallen below the MIC value.
* Corresponding author. Tel: +39-02-70146363; Fax: +39-02-70146371.
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