Sub-MIC concentrations of cefodizime interfere with various factors affecting bacterial virulence.
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.
Braga
P C
PC
Department of Pharmacology, School of Medicine, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Sasso
M D
MD
Sala
M T
MT
D001422:Bacterial Adhesion / Q000187:drug effects; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002511:Cephalosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology; D009068:Movement / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
D002511:Cephalosporins; D002439:Cefotaxime; C033356:cefodizime