Cefodizime as a biological response modifier: a review of its in-vivo, ex-vivo and in-vitro immunomodulatory properties

Immunomodulation by antibacterial agents shows promise as a novel strategy in the treatment of infectious diseases. Cefodizime, a new oxi-imino-amino-2-thiazolyl cephalosporin, is a particularly good candidate in this context. In-vivo models of experimental infections show that prophylactic administration of cefodizime increases the survival of some strains of mice after challenge with Toxoplasma gondii</it> or Candida albicans</it>; its curative effect in infections due to members of the Enterobacteriaceae is better than that expected from in-vitro MIC determinations relative to other third-generation cephalosporins; this effect is even more marked in immuno-compromised animals. Data obtained both in vivo</it> and ex vivo</it> show that cefodizime enhances various immune parameters such as phagocyte function, B lymphocyte responsiveness and delayed hypersensitivity; it may restore natural killer (NK) and phagocyte activity, as well as interleukin 1 (IL-1) and interferon production, in immunocompromised patients and animals. The in-vitro effects of this drug include enhancement of phagocyte bactericidal activity and alteration of bacterial virulence factors. The chemical basis for these various immunomodulatory properties is related to the thio-thiazolyl side-chain at position 3 of the cephem nucleus. To date, the mechanisms underlying the immunomodulatory properties of cefodizime have not been identified clearly, but it is likely that it interferes at different levels of specific and non-specific immune defences.