MICROBIOLOGICAL ASPECTS OF ANTIBIOTICS WI TH IMMUNODULATING ACTIVITY

Through the introduction of a 7-mercapto-1,3-thiazole chain at positio n 3' of the dihydrothiazine ring, cefodizime, which is structurally si milar to cefotaxime, has acquired a number of remarkable immunomodulat ory properties while retaining a potent antimicrobial spectrum of acti vity. Cefodizime penetrates in fact readily through the bacterial cell wall and interacts with its molecular targets in such a way that at h igh concentrations cell death and lysis are rapidly induced. Its spect rum of action encompasses the Enterobacteria, Neisseriae, Haemophilus, Moraxella catarrhalis, methicillin-susceptible staphylococci and stre ptococci, with pneumococci included. Cefodizime is devoid of useful po tency against Pseudomonas, Acinetobacter and enterococci. Given the wi de occurrence of strains synthesizing beta-lactamases in several prima ry pathogens of community-acquired and nosocomial infections, the comp lete stability of cefodizime towards the most prevalent of these hydro lytic enzymes (TEM-1, TEM-2, SHV-1, BRO-1 and the staphylococcal penic illinases) seems reassuring. Only a few chromosomally-coded and extend ed spectrum beta-lactamases produced by gram-negative microorganisms i nactivate the new cephalosporin. Since the distribution of pathogens c arrying these enzymes depends on the local trends of antibacterial con sumption and cannot be easily predicted, a large multicenter study in Italy has recently assessed the antibacterial potency of cefodizime, i n comparison with suitable drugs, on 1985 selected nosocomial strains. In this survey cefodizime was more effective in vitro than amoxicilli n-clavulanate, gentamicin and piperacillin while being substantially s imilar in the rates of eradication of gram-negative and gram-positive organisms to other third generation cephalosporins like ceftazidime an d ceftriaxone. These results confirm that cefodizime, because of its a ppropriate antibacterial spectrum, lack of resistance in primary patho gens and original immunomodulatory properties may find a role in the m anagement of hospital infections.