EXPERIMENTAL EVALUATION OF ANTIBIOTICS AS IMMUNOMODULATORS

Since the pioneer work by Metchnikoff, the goal of cooperation between therapeutics and the host defence system (HDS) has been sought after. This area of research received less attention after the introduction of antibiotics. Although, the predictive efficacy of antibacterial age nts (ABA) is still evaluated in terms of MICs, MBCs, and pharmacokinet ics, much evidence derived from clinical studies underlines the need f or synergy between HDS and these drugs to obtain optimal therapeutic e fficacy. The analysis of the immunomodifying properties of ABA has com e under intense study. The majority of ABA does not substantially affe ct the functioning of the immune system at least in vivo, despite in-v itro observations of enhancement/inhibition of various immune paramete rs by some cephalosporins, macrolides, cyclines, aminoglycosides, etc. By contrast, chloramphenicol, sulphonamides and various beta-lactams may be responsible for drug-induced neutropenia whereas macrolides and quinolones, due to their high phagocytic uptake, synergize with phago cytes to destroy intracellular pathogens. Recently, the concept of Bio logical Response Modifier (BRM)-antibiotics has come under the limelig ht with the introduction of cefodizime, a new parenteral cephalosporin , which seems to be endowed with immunomodulating properties. This lat ter aspect has been demonstrated in vitro (potentiation of the phagocy te antimicrobial activity), ex vivo in immunocompromised animals and h umans (restoration of various immune parameters) and in vivo (infectio n models using both sensitive and resistant species). Although the und erlying mechanism has not been elucitated, the chemical structure resp onsible for this BRM activity has been recognized as the thio-thiazoly l moiety at C3 position of the cephem nucleus. That cefodizime becomes a leading drug in the field of BRM-antibiotics should raise new hopes in the treatment of infectious diseases.