Comparison of cefodizime with various cephalosporins for their indirect effect on the human neutrophil oxidative burst in vitro.

Cefodizime, a 2-amino-thiazolyl cephalosporin, is reported to display in-vitro, ex-vivo and in-vivo immunomodulatory properties; in particular, it enhances the survival of mice infected with cefodizime-resistant pathogens. We have used an in-vitro model to assess the indirect effect of this drug (compared with other cephalosporins) on the neutrophil (PMN) oxidative response. Pseudomonas aeruginosa was employed as the bacterial target for cefodizime and cefotaxime (MICs greater than 128 mg/l), cefsulodin (MIC 16 mg/l) and ceftazidime (MIC 32 mg/l). After overnight growth in the presence of subinhibitory concentrations of each drug (10 mg/l), the altered filamentous P. aeruginosa induced a stronger oxidative response of PMN than untreated control bacteria. For all cephalosporins this was related to alterations of bacterial structure leading to increased deposits of antibodies and/or complement. Furthermore, increased non-opsonin dependent stimulation of the PMN oxidative burst was obtained; the strongest response was observed with cefodizime-treated P. aeruginosa in the case of low responder PMN, which displayed a deficient response after stimulation by control bacteria. The possibility that cefodizime could enhance this PMN function in opsonin-deficient patients requires further investigation.