Effect of antibiotic sub inhibitory concentration on cytolethal distending toxin production by Campylobacter jejuni

To investigate the effect of pre-exposure antibiotics on cytolethal distending toxin (CDT) production and toxigenic effect of C. jejuni.Sonicates and filtrates were prepared from known cdt+ and cdt- isolates of C. jejuni which had been pre-exposed to varying concentrations (MIC, 1/2 MIC, 1/4 MIC, 1/8 MIC) of erythromycin and ciprofloxacin. The CDT toxigenic effect was examined using INT 407 and HeLa cells.A trend of increased toxigenic effect was observed with pre-exposure to antibiotics. This was more pronounced with erythromycin pre-exposure compared to ciprofloxacin. Although a trend of increasing toxigenic effect with decreasing antibiotic concentration was demonstrable, some differences were observed between isolates. In one isolate the increased toxigenic effect was statistically significant (P<0.05) at 1/4 MIC in INT 407 cells and at 1/8 MIC in HeLa cells.This study provides evidence of an association between CDT production by C. jejuni and pre-exposure to antibiotics. Pre-exposure to ciprofloxacin and erythromycin at concentrations below MICs could potentiate CDT activity. Further work is needed to elucidate the mechanism involved. We recommend that these antibiotics be used in the treatment of C. jejuni enteritis only when strongly indicated and with careful monitoring of patients.