Cefotaxime and its desacetoxymethyl derivative, ceftizoxime (previously known as FK749), are both extremely active against a wide spectrum of bacteria. In the present comparative study, the activity of ceftizoxime exceeded that of cefotaxime by a factor of four or more for strains of Klebsiella, Enterobacter, Providencia, Serratia, and Bacteroides; the only species for which the activity of cefotaxime exceeded that of ceftizoxime by a factor of four was Vibrio cholerae. Against other species, the activity of the two drugs was roughly comparable. Both showed outstanding activity against Haemophilus influenzae and Neisseriagonorrhoeae. Comparative turbidimetric and morphological studies revealed that ceftizoxime was able to induce spheroplast formation and rapid lysis in Escherichia coli strains at lower concentrations than cefotaxime. This difference was not found, however, when E. coli strains resistant to ampicillin by an intrinsic (nonenzymic) mechanism were tested.During the last few years, so-called "new-generation" injectable cephalosporins have emerged which are characterized by outstanding resistance to most f8-lactamases. Prominent among these are cefuroxime (10) and the cephamycin antibiotic, cefoxitin (11), both of which are now in clinical use. The resistance of these new agents to enzymic destruction considerably broadens their antibacterial spectrum, but their intrinsic antibacterial activity is, in itself, relatively modest. More recently, a new cephalosporin, cefotaxime, has been described (1, 6, 7) which combines enzyme stability with high intrinsic activity against all but a few bacterial species. Attempts to further improve on this activity have led to the development in Japan of the desacetoxymethyl derivative of cefotaxime, ceftizoxime ( Fig. 1) Turbidimetric studies. Four strains of Escherichia coli were investigated. These were chosen from laboratory stock cultures to represent (i) an ampicillinsensitive strain, (ii) a strain resistant to ampicillin by virtue of an R-TEM-type ,B-lactamase, (iii) two strains resistant to ,B-lactam antibiotics by an intrinsic (nonenzymic) mechanism.Cultures were grown from small inocula in "complete" broth (3) in a modified version (C. Aldridge, M.Sc. thesis, University of London, London, England, 1975) of the multichannel bacterial growth monitoring device described by Mackintosh et al. (8), in which the opacity of 12 independent bacterial cultures could be continuously recorded. Antibiotic was added at a standard point in the logarithmic growth phase (36% maximum opacity) equivalent to a viable count df ca. 5 x 107 bacteria per ml.Microscopy. Observations of antibiotic-induced morphological changes in broth cultures of bacteria were made after a 1-h exposure to antibiotic by interference-contrast microscopy.Bladder model. The design and operation of the in vitro bladder model have been described in detail elsewhere (5). In the present experiments, 20 ml of an overnight broth culture of E. coli was diluted with fresh broth at a rate of 1 ml per min (the no...